首页 > 最新文献

Experimental and molecular pathology最新文献

英文 中文
A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options 基于免疫基因组景观分析和免疫治疗方案的胃腺癌新的预后指标
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104832
Weijie Xue , Bingzi Dong , Yixiu Wang , Yuwei Xie , Pu Li , Zhiqi Gong , Zhaojian Niu

Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) treatment. Transcriptome, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a Cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas monocytes, M2 macrophages, eosinophils, and neutrophils were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy in patients with STAD.

胃腺癌(STAD)是全球最常见的恶性肿瘤之一。在本研究中,我们试图构建一个有效的免疫相关基因预后指数风险模型,该模型可以预测STAD患者的生存和免疫检查点抑制剂(ici)治疗的疗效。转录组、临床和基因突变数据来自TCGA数据库。从import和InnateDB数据库下载免疫相关基因。共鉴定出493个免疫相关基因,这些基因在与免疫应答相关的功能以及免疫和肿瘤相关途径中富集。进一步,通过加权基因共表达网络分析(WGCNA)获得36个与STAD总生存期(OS)相关的候选基因。接下来,在Cox回归分析的基础上,我们构建了基于8个基因的免疫相关基因预后指数(IAGPI)风险模型,并使用GEO STAD队列进行验证。根据患者的风险评分将患者分为两个亚组。低危组患者的OS优于高危组。低危组CD8、活化记忆CD4、滤泡辅助性T细胞、M1巨噬细胞较多,高危组单核细胞、M2巨噬细胞、嗜酸性粒细胞、中性粒细胞较多。低危组患者对ICIs治疗更敏感。IAGPI风险模型可以准确预测预后,反映肿瘤免疫微环境,预测ICIs治疗STAD患者的疗效。
{"title":"A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options","authors":"Weijie Xue ,&nbsp;Bingzi Dong ,&nbsp;Yixiu Wang ,&nbsp;Yuwei Xie ,&nbsp;Pu Li ,&nbsp;Zhiqi Gong ,&nbsp;Zhaojian Niu","doi":"10.1016/j.yexmp.2022.104832","DOIUrl":"10.1016/j.yexmp.2022.104832","url":null,"abstract":"<div><p>Stomach adenocarcinoma<span><span><span><span> (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) </span>treatment. </span>Transcriptome<span><span>, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a </span>Cox regression<span><span><span> analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8<span>, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas </span></span>monocytes, M2 macrophages, </span>eosinophils<span>, and neutrophils<span> were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy </span></span></span></span></span>in patients with STAD.</span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104832"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10328775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Microbial community profiling by next-generation DNA sequencing of adenocarcinoma of the prostate with evidence of ochratoxin A producing fungi 利用下一代DNA测序分析前列腺腺癌的微生物群落特征和赭曲霉毒素A产生真菌的证据
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104831
Stephen E. Fry , Mitchell Kaye , Dara S. Missan , Christian Becker , Matthew Shabilla , Delyn Martinez , Erin Bossert , Jeremy Ellis

Background

Prostatic carcinomas are a leading cancer and leading cause of mortality in the developed world. The etiology is diverse with underlying patient genetics, environmental factors, and microbial associations. Sequencing DNA for microbes allows the detection of potential disease relationships.

Objective

Targeted 16S (prokaryotic) and 18S (eukaryotic) rDNA sequencing was performed to map the tumor microbial flora.

Design

Twelve patients undergoing elective laparoscopic prostatectomy for biopsy proven adenocarcinoma of the prostate were enrolled. PCR and amplicon based sequencing was conducted; a portion of the sequencing results were confirmed by special stains.

Setting

Patients were recruited by the urologist were prospectively scheduled for radical prostatectomy by ‘Da Vinci’ robotically assisted procedure in an outpatient setting. Samples were portioned in the hospital surgical suite at the time of prostatectomy.

Participants

Male patients were requested to enter the study on a first come basis. Outcome Measurement and Statistical Analysis: Average age of the 12 participants was 64.3 years.

Results and limitations

DNA reads were detected and by ‘best match’ were identified belonging to Perkinsus, Hydrurus, Diversispora and Funneliformis genera, few samples displayed bacteria. Out of the 12 total patients, 11 patients had detectable DNA sequences matching arbuscular mycorrhizal fungi in the Glomeromycetes Class; Funneliformis mosseae and Diversasporum versiformis. Specific PCR for arbuscular mycorrhizal fungi failed to confirm Glomeromycetes Class; in-depth taxonomic analysis suggests a newer fungal grouping, not falling within an accepted Phylum of fungi. Calcoflour white staining of histological sections confirmed potential fungal markers in all 12 cases. Ochratoxin A antigen was identified by immunofluorescence in all 12 patient samples. The study was limited by the low sample volume and disease free normal controls.

Conclusions

Fungi may play a significant role in adenocarcinoma of the prostate.

背景:前列腺癌是发达国家的主要癌症和主要死亡原因。病因多样,有潜在的患者遗传、环境因素和微生物关联。微生物的DNA测序可以检测潜在的疾病关系。目的对肿瘤微生物区系进行16S(原核)和18S(真核)rDNA靶向测序。12例经活检证实为前列腺腺癌的患者接受择期腹腔镜前列腺切除术。采用PCR和扩增子测序;部分测序结果经特殊染色证实。由泌尿科医生招募的患者在门诊接受“达芬奇”机器人辅助手术进行根治性前列腺切除术。在前列腺切除术时,样本在医院外科套房中进行分配。参与者:小患者被要求以先到为基础进入研究。结果测量与统计分析:12例患者平均年龄64.3岁。结果与限制检测了dna读数,并通过“最佳匹配”鉴定出属于Perkinsus, Hydrurus, diverspora和funeliformis属,少数样品显示细菌。在12例患者中,11例患者检测到与肾小球菌类丛枝菌根真菌相匹配的DNA序列;苔藓漏斗孢和异形孢。丛枝菌根真菌的特异性PCR不能确定肾小球菌属;深入的分类学分析表明,这是一种较新的真菌类群,不属于公认的真菌门。组织切片钙粉白染色证实了所有12例病例中潜在的真菌标志物。12例患者标本均经免疫荧光法鉴定出赭曲霉毒素A抗原。该研究受到样本量少和无疾病正常对照的限制。结论真菌可能在前列腺腺癌的发生中起重要作用。
{"title":"Microbial community profiling by next-generation DNA sequencing of adenocarcinoma of the prostate with evidence of ochratoxin A producing fungi","authors":"Stephen E. Fry ,&nbsp;Mitchell Kaye ,&nbsp;Dara S. Missan ,&nbsp;Christian Becker ,&nbsp;Matthew Shabilla ,&nbsp;Delyn Martinez ,&nbsp;Erin Bossert ,&nbsp;Jeremy Ellis","doi":"10.1016/j.yexmp.2022.104831","DOIUrl":"10.1016/j.yexmp.2022.104831","url":null,"abstract":"<div><h3>Background</h3><p>Prostatic carcinomas are a leading cancer and leading cause of mortality in the developed world. The etiology is diverse with underlying patient genetics, environmental factors, and microbial associations. Sequencing DNA for microbes allows the detection of potential disease relationships.</p></div><div><h3>Objective</h3><p>Targeted 16S (prokaryotic) and 18S (eukaryotic) rDNA sequencing was performed to map the tumor microbial flora.</p></div><div><h3>Design</h3><p>Twelve patients undergoing elective laparoscopic prostatectomy for biopsy proven adenocarcinoma of the prostate were enrolled. PCR and amplicon based sequencing was conducted; a portion of the sequencing results were confirmed by special stains.</p></div><div><h3>Setting</h3><p>Patients were recruited by the urologist were prospectively scheduled for radical prostatectomy by ‘Da Vinci’ robotically assisted procedure in an outpatient setting. Samples were portioned in the hospital surgical suite at the time of prostatectomy.</p></div><div><h3>Participants</h3><p>Male patients were requested to enter the study on a first come basis. Outcome Measurement and Statistical Analysis: Average age of the 12 participants was 64.3 years.</p></div><div><h3>Results and limitations</h3><p>DNA reads were detected and by ‘best match’ were identified belonging to Perkinsus, Hydrurus, Diversispora and Funneliformis genera, few samples displayed bacteria. Out of the 12 total patients, 11 patients had detectable DNA sequences matching arbuscular mycorrhizal fungi in the Glomeromycetes Class; Funneliformis mosseae and Diversasporum versiformis. Specific PCR for arbuscular mycorrhizal fungi failed to confirm Glomeromycetes Class; in-depth taxonomic analysis suggests a newer fungal grouping, not falling within an accepted Phylum of fungi. Calcoflour white staining of histological sections confirmed potential fungal markers in all 12 cases. Ochratoxin A antigen was identified by immunofluorescence in all 12 patient samples. The study was limited by the low sample volume and disease free normal controls.</p></div><div><h3>Conclusions</h3><p>Fungi may play a significant role in adenocarcinoma of the prostate.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104831"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000946/pdfft?md5=e7aa9fd3770a6f4078827dd710806fca&pid=1-s2.0-S0014480022000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Value of immunohistochemistry in crushed areas of pulmonary neuroendocrine carcinoma 免疫组织化学在肺神经内分泌癌粉碎区的价值
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104836
Hava Kuçuk , David Laville , Pierre Dal-Col , Violaine Yvorel , Abdulrazzak Sulaiman , Sophie Bayle-Bleuez , Philippe Cosmo , Jean-Michel Vergnon , Olivier Tiffet , Anne-Laure Desage , Fabien Forest

Immunohistochemical demonstration of neuroendocrine differentiation is often performed in routine diagnostic practice for lung neuroendocrine carcinoma. However, these carcinomas are often crushed, especially on small specimens. The value of immunohistochemistry on crushed areas is not known. We aimed to assess the value of immunohistochemical markers in crushed areas. We performed a retrospective study of 299 patients with a diagnosis of pulmonary neuroendocrine carcinoma. We showed that the markers TTF-1, synaptophysin, chromogranin A, CD56, and INSM1 were more often negative in crushed areas compared with well-preserved areas. The proliferation index with anti-Ki67 was decreased but remained on average around 90%. For all markers, the percentage of labeled cells was lower than in the preserved areas. Finally, we show that cases without labeling in the crushed areas and maintained labeling in the non-crushed areas have a lower percentage of labeling than cases without this labeling mismatch. Finally, there were no false positives of these stains.

Neuroendocrine markers are valid in crushed areas when positive. However, the percentage of labeled cells may be lower than on preserved areas and lead to false negatives. Finally, the proliferation index, although decreased, remains close to that on preserved areas.

神经内分泌分化的免疫组化证实是肺神经内分泌癌的常规诊断方法。然而,这些癌经常被粉碎,特别是在小样本上。免疫组织化学对压碎区域的价值尚不清楚。我们的目的是评估免疫组织化学标记物在压碎区域的价值。我们对299例诊断为肺神经内分泌癌的患者进行了回顾性研究。我们发现TTF-1、synaptophysin、chromogranin A、CD56和INSM1标记物在压碎区比保存完好的区域更常呈阴性。抗ki67的增殖指数下降,但平均保持在90%左右。对于所有标记物,标记细胞的百分比低于保存区域。最后,我们表明,在碾碎区域没有标签的情况下,在非碾碎区域保持标签比没有这种标签不匹配的情况下有更低的标签百分比。最后,这些染色没有假阳性。神经内分泌标志物在压碎区阳性时有效。然而,标记细胞的百分比可能低于保存区域,导致假阴性。最后,增殖指数虽有所下降,但仍与保护区相近。
{"title":"Value of immunohistochemistry in crushed areas of pulmonary neuroendocrine carcinoma","authors":"Hava Kuçuk ,&nbsp;David Laville ,&nbsp;Pierre Dal-Col ,&nbsp;Violaine Yvorel ,&nbsp;Abdulrazzak Sulaiman ,&nbsp;Sophie Bayle-Bleuez ,&nbsp;Philippe Cosmo ,&nbsp;Jean-Michel Vergnon ,&nbsp;Olivier Tiffet ,&nbsp;Anne-Laure Desage ,&nbsp;Fabien Forest","doi":"10.1016/j.yexmp.2022.104836","DOIUrl":"10.1016/j.yexmp.2022.104836","url":null,"abstract":"<div><p><span>Immunohistochemical demonstration of neuroendocrine differentiation is often performed in routine diagnostic practice for lung </span>neuroendocrine carcinoma<span><span><span>. However, these carcinomas are often crushed, especially on small specimens. The value of immunohistochemistry on crushed areas is not known. We aimed to assess the value of immunohistochemical markers in crushed areas. We performed a retrospective study of 299 patients with a diagnosis of pulmonary neuroendocrine carcinoma. We showed that the markers TTF-1, </span>synaptophysin, </span>chromogranin A, CD56, and INSM1 were more often negative in crushed areas compared with well-preserved areas. The proliferation index with anti-Ki67 was decreased but remained on average around 90%. For all markers, the percentage of labeled cells was lower than in the preserved areas. Finally, we show that cases without labeling in the crushed areas and maintained labeling in the non-crushed areas have a lower percentage of labeling than cases without this labeling mismatch. Finally, there were no false positives of these stains.</span></p><p>Neuroendocrine markers are valid in crushed areas when positive. However, the percentage of labeled cells may be lower than on preserved areas and lead to false negatives. Finally, the proliferation index, although decreased, remains close to that on preserved areas.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104836"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Sulfur mustard corneal injury is associated with alterations in the epithelial basement membrane and stromal extracellular matrix 硫芥角膜损伤与上皮基底膜和基质细胞外基质的改变有关。
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104807
Laurie B. Joseph , Marion K. Gordon , Peihong Zhou , Rita A. Hahn , Hamdi Lababidi , Claire R. Croutch , Patrick J. Sinko , Diane E. Heck , Debra L. Laskin , Jeffrey D. Laskin

Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional alkylating agent synthesized for chemical warfare. The eyes are particularly sensitive to SM where it causes irritation, pain, photophobia, and blepharitis, depending on the dose and duration of exposure. In these studies, we examined the effects of SM vapor on the corneas of New Zealand white male rabbits. Edema and hazing of the cornea, signs of acute injury, were observed within one day of exposure to SM, followed by neovascularization, a sign of chronic or late phase pathology, which persisted for at least 28 days. Significant epithelial-stromal separation ranging from ~8–17% of the epithelial surface was observed. In the stroma, there was a marked increase in CD45+ leukocytes and a decrease of keratocytes, along with areas of disorganization of collagen fibers. SM also disrupted the corneal basement membrane and altered the expression of perlecan, a heparan sulfate proteoglycan, and cellular fibronectin, an extracellular matrix glycoprotein. This was associated with an increase in basement membrane matrix metalloproteinases including ADAM17, which is important in remodeling of the basement membrane during wound healing. Tenascin-C, an extracellular matrix glycoprotein, was also upregulated in the stroma 14–28 d post SM, a finding consistent with its role in organizing structural components of the stroma necessary for corneal transparency. These data demonstrate that SM vapor causes persistent alterations in structural components of the cornea. Further characterization of SM-induced injury in rabbit cornea will be useful for the identification of targets for the development of ocular countermeasures.

硫芥(SM;双(2-氯乙基)硫化物)是一种用于化学战的高活性双功能烷基化剂。眼睛对SM特别敏感,根据暴露的剂量和持续时间,SM会引起刺激、疼痛、畏光和睑缘炎。在这些研究中,我们检测了SM蒸汽对新西兰雄性大白鼠角膜的影响。在暴露于SM的一天内,观察到角膜水肿和模糊,这是急性损伤的迹象,随后是新生血管形成,这是慢性或晚期病理的迹象,持续了至少28天。观察到明显的上皮-基质分离,范围为上皮表面的~8-17%。在基质中,CD45+白细胞显著增加,角化细胞减少,胶原纤维紊乱。SM还破坏了角膜基底膜,并改变了perlecan(一种硫酸乙酰肝素蛋白多糖)和细胞纤连蛋白(一种细胞外基质糖蛋白)的表达。这与包括ADAM17在内的基底膜基质金属蛋白酶的增加有关,ADAM17在伤口愈合过程中对基底膜的重塑很重要。Tenascin-C,一种细胞外基质糖蛋白,在SM后14-28天在基质中也上调,这一发现与其在组织角膜透明所需的基质结构成分中的作用一致。这些数据表明SM蒸汽会导致角膜结构成分的持续变化。SM诱导的兔角膜损伤的进一步表征将有助于确定眼部对抗措施的靶点。
{"title":"Sulfur mustard corneal injury is associated with alterations in the epithelial basement membrane and stromal extracellular matrix","authors":"Laurie B. Joseph ,&nbsp;Marion K. Gordon ,&nbsp;Peihong Zhou ,&nbsp;Rita A. Hahn ,&nbsp;Hamdi Lababidi ,&nbsp;Claire R. Croutch ,&nbsp;Patrick J. Sinko ,&nbsp;Diane E. Heck ,&nbsp;Debra L. Laskin ,&nbsp;Jeffrey D. Laskin","doi":"10.1016/j.yexmp.2022.104807","DOIUrl":"10.1016/j.yexmp.2022.104807","url":null,"abstract":"<div><p><span><span>Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a highly reactive bifunctional </span>alkylating agent<span> synthesized for chemical warfare. The eyes are particularly sensitive to SM where it causes irritation, pain, photophobia<span><span>, and blepharitis, depending on the dose and duration of exposure. In these studies, we examined the effects of SM vapor on the corneas of New Zealand white male rabbits. Edema and hazing of the cornea, signs of acute injury, were observed within one day of exposure to SM, followed by </span>neovascularization<span>, a sign of chronic or late phase pathology, which persisted for at least 28 days. Significant epithelial-stromal separation ranging from ~8–17% of the epithelial surface was observed. In the stroma, there was a marked increase in CD45</span></span></span></span><sup>+</sup><span><span><span><span> leukocytes and a decrease of keratocytes<span><span><span>, along with areas of disorganization of collagen fibers. SM also disrupted the corneal </span>basement membrane and altered the expression of </span>perlecan, a </span></span>heparan sulfate </span>proteoglycan, and cellular </span>fibronectin<span>, an extracellular matrix<span> glycoprotein<span><span>. This was associated with an increase in basement membrane matrix metalloproteinases including </span>ADAM17, which is important in remodeling of the basement membrane during wound healing. Tenascin-C, an extracellular matrix glycoprotein, was also upregulated in the stroma 14–28 d post SM, a finding consistent with its role in organizing structural components of the stroma necessary for corneal transparency. These data demonstrate that SM vapor causes persistent alterations in structural components of the cornea. Further characterization of SM-induced injury in rabbit cornea will be useful for the identification of targets for the development of ocular countermeasures.</span></span></span></span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104807"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Serum levels of matrix metalloproteinases as prognostic markers for severe dengue with plasma leakage 血清基质金属蛋白酶水平作为重症登革热伴血浆渗漏的预后指标
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104821
Srinivasan Sivasubramanian , Sundhar Mohandas , Vidya Gopalan , Karthikeyan Govindan , Poovazhagi Varadarajan , Krishnasamy Kaveri , Kunka Mohanram Ramkumar

Background

Plasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage.

Methods

The dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay.

Results

MMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients.

Conclusion

MMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.

背景血浆渗漏是重症登革热的主要致病表现,是与登革热相关的危及生命的并发症的前兆。越来越多的证据表明基质金属蛋白酶(MMPs)在登革热病毒诱导后介导血管通透性和血浆渗漏中的作用。本研究旨在探讨MMP-2、MMP-3和MMP-9在预测登革热感染严重程度中的作用,并进一步探讨这些标志物与血浆渗漏相关致病因素的关系。方法将登革热阳性人群根据症状表现分为轻、重度登革热组。对各组标本及健康对照进行基本实验室特征定量分析。使用基于多重头部的测定法估计所有血清样品中MMP-2、MMP-3、MMP-9和巨噬细胞迁移抑制因子(MIF)的水平。结果重症登革热患者血清smmp -2和MMP-9水平明显高于轻症患者和健康对照。在研究组之间没有观察到循环中MMP-3水平的变化。ROC曲线分析显示,MMP-2和MMP-9具有较好的预测重症登革热的潜力。值得注意的是,在严重登革热患者中,MMP-9的增加与MIF和红细胞压积水平的增加有关。结论mmp -2和MMP-9可作为重症登革热的预后生物标志物。这些发现还确定了MMP-9与血浆渗漏标志物的关联,从而鼓励进一步研究探索靶向MMP-9治疗重症登革热血浆渗漏的治疗潜力。
{"title":"Serum levels of matrix metalloproteinases as prognostic markers for severe dengue with plasma leakage","authors":"Srinivasan Sivasubramanian ,&nbsp;Sundhar Mohandas ,&nbsp;Vidya Gopalan ,&nbsp;Karthikeyan Govindan ,&nbsp;Poovazhagi Varadarajan ,&nbsp;Krishnasamy Kaveri ,&nbsp;Kunka Mohanram Ramkumar","doi":"10.1016/j.yexmp.2022.104821","DOIUrl":"10.1016/j.yexmp.2022.104821","url":null,"abstract":"<div><h3>Background</h3><p>Plasma leakage is a major pathogenic manifestation of severe dengue<span><span> and is a precursor of life-threatening complications associated with dengue<span>. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating </span></span>vascular permeability<span> and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage.</span></span></p></div><div><h3>Methods</h3><p>The dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay.</p></div><div><h3>Results</h3><p>MMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients.</p></div><div><h3>Conclusion</h3><p>MMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104821"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
MicroRNA-575 acts as a novel oncogene via targeting multiple signaling pathways in glioblastoma MicroRNA-575在胶质母细胞瘤中作为一种新的致癌基因,通过靶向多种信号通路发挥作用
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104813
Ashley Gray , Tiantian Cui , Erica Hlavin Bell , Joseph McElroy , Ebin Sebastian , Fuhai Li , Marjolein Geurts , Kevin Liu , Pierre Robe , S. Jaharul Haque , Arnab Chakravarti

Purpose

Glioblastoma (GBM) patients currently face poor survival outcomes with an average survival period of <15 months, while only 3–5% of patients survive longer than 36 months. Although the mechanisms of tumorigenesis are still being elucidated, miRNAs are promising candidates to explore as novel and prognostic biomarkers in GBM. In this study, we identified the association between miR-575 expression and overall survival (OS) of primary GBM patients and undertook functional studies to discern the contribution of miR-575 to GBM tumorigenesis.

Methods

Total RNAs were isolated from 254 FFPE GBM tumor samples and miR expression was assayed (simultaneously) using NanoString Technologies. To determine the association between miR-575 and patients' prognosis, Kaplan-Meier, univariable and multivariable Cox regression analyses were performed. Cell proliferation, colony formation, migration assays were conducted to investigate the function of miR-575 in vitro and in vivo. In silico target gene network analysis was performed to identify the putative targets of miR-575 in GBM, which were further verified by luciferase reporter assay, as well as qPCR and immunoblotting.

Results

Our clinical data (n = 254) show that miR-575 is associated with worse GBM OS by univariable analysis (UVA, HR = 1.27, p-value<0.001) and multivariable (MVA, HR = 1.23, p = 0.007) analysis incorporating critical clinical variables. Functional studies indicated that overexpression of miR-575 significantly increased cell proliferation and migration of GBM cells in vitro, as well as tumor growth in vivo. Subsequent in silico target gene network and mechanistic studies identified CDKN1B/p27 and PTEN, as potential targets of miR-575 in GBM. MicroRNA-575 can also regulate the activity of AKT and ERK pathways in GBM.

Conclusion

miR-575 has prognostic value in GBM, with higher expression associating with worse OS of patients, and contributes to GBM tumorigenesis by regulating multiple signaling pathways in GBM.

目的胶质母细胞瘤(GBM)患者目前面临较差的生存结果,平均生存期为15个月,而只有3-5%的患者存活时间超过36个月。尽管肿瘤发生的机制仍未被阐明,但mirna有望作为GBM的新型和预后生物标志物进行探索。在这项研究中,我们确定了miR-575表达与原发性GBM患者总生存期(OS)之间的关联,并进行了功能研究,以确定miR-575对GBM肿瘤发生的贡献。方法从254例FFPE GBM肿瘤中分离总rna,同时利用NanoString技术检测miR的表达。为了确定miR-575与患者预后的关系,我们进行Kaplan-Meier、单变量和多变量Cox回归分析。通过细胞增殖、集落形成、迁移实验研究miR-575在体外和体内的功能。通过计算机靶基因网络分析来确定miR-575在GBM中的推测靶点,并通过荧光素酶报告基因实验、qPCR和免疫印迹法进一步验证。结果我们的临床数据(n = 254)显示,单变量分析(UVA, HR = 1.27, p值<0.001)和包含关键临床变量的多变量分析(MVA, HR = 1.23, p = 0.007)表明,miR-575与较差的GBM OS相关。功能研究表明,过表达miR-575可显著增加体外GBM细胞的增殖和迁移,以及体内肿瘤的生长。随后的硅靶基因网络和机制研究发现CDKN1B/p27和PTEN是miR-575在GBM中的潜在靶点。MicroRNA-575还可以调节GBM中AKT和ERK通路的活性。结论mir -575在GBM中具有预后价值,表达水平越高,患者OS越差,mir -575通过调节GBM中多种信号通路参与GBM的发生。
{"title":"MicroRNA-575 acts as a novel oncogene via targeting multiple signaling pathways in glioblastoma","authors":"Ashley Gray ,&nbsp;Tiantian Cui ,&nbsp;Erica Hlavin Bell ,&nbsp;Joseph McElroy ,&nbsp;Ebin Sebastian ,&nbsp;Fuhai Li ,&nbsp;Marjolein Geurts ,&nbsp;Kevin Liu ,&nbsp;Pierre Robe ,&nbsp;S. Jaharul Haque ,&nbsp;Arnab Chakravarti","doi":"10.1016/j.yexmp.2022.104813","DOIUrl":"10.1016/j.yexmp.2022.104813","url":null,"abstract":"<div><h3>Purpose</h3><p>Glioblastoma<span> (GBM) patients currently face poor survival outcomes with an average survival period of &lt;15 months, while only 3–5% of patients survive longer than 36 months. Although the mechanisms of tumorigenesis are still being elucidated, miRNAs are promising candidates to explore as novel and prognostic biomarkers in GBM. In this study, we identified the association between miR-575 expression and overall survival (OS) of primary GBM patients and undertook functional studies to discern the contribution of miR-575 to GBM tumorigenesis.</span></p></div><div><h3>Methods</h3><p><span><span>Total RNAs were isolated from 254 FFPE GBM tumor samples and miR expression was assayed (simultaneously) using NanoString Technologies. To determine the association between miR-575 and patients' prognosis, Kaplan-Meier, univariable and multivariable </span>Cox regression<span> analyses were performed. Cell proliferation, colony formation, migration assays were conducted to investigate the function of miR-575 </span></span><em>in vitro</em> and <em>in vivo</em>. <span><em>In silico</em></span><span><span> target gene network analysis was performed to identify the putative targets of miR-575 in GBM, which were further verified by luciferase reporter assay, as well as qPCR and </span>immunoblotting.</span></p></div><div><h3>Results</h3><p>Our clinical data (<em>n</em> = 254) show that miR-575 is associated with worse GBM OS by univariable analysis (UVA, HR = 1.27, <em>p</em>-value&lt;0.001) and multivariable (MVA, HR = 1.23, <em>p</em> = 0.007) analysis incorporating critical clinical variables. Functional studies indicated that overexpression of miR-575 significantly increased cell proliferation and migration of GBM cells <em>in vitro</em>, as well as tumor growth <em>in vivo</em>. Subsequent <em>in silico</em> target gene network and mechanistic studies identified CDKN1B/p27 and PTEN, as potential targets of miR-575 in GBM. MicroRNA-575 can also regulate the activity of AKT and ERK pathways in GBM.</p></div><div><h3>Conclusion</h3><p>miR-575 has prognostic value in GBM, with higher expression associating with worse OS of patients, and contributes to GBM tumorigenesis by regulating multiple signaling pathways in GBM.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104813"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10702393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Targeted molecular profiling of epithelial ovarian cancer from Italian BRCA wild-type patients with a BRCA and PARP pathways gene panel 具有BRCA和PARP通路基因面板的意大利BRCA野生型患者上皮性卵巢癌的靶向分子谱分析
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104833
Annamaria Salvati , Ileana Carnevali , Elena Alexandrova , Sofia Facchi , Susanna Ronchi , Laura Libera , Nora Sahnane , Domenico Memoli , Jessica Lamberti , Sonia Amabile , Stefano Pepe , Roberta Tarallo , Fausto Sessa , Alessandro Weisz , Maria Grazia Tibiletti , Francesca Rizzo

Ovarian cancer (OC) is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. Identification of pathogenic variants in OC tissues has an important clinical significance for therapeutic and prevention purposes. This study aims to evaluate the mutational profile of a patient cohort, negative for BRCA1/2 germinal variants and Mismatch Repair defects, using next-generation sequencing (NGS) approach on DNA from formalin-fixed paraffin-embedded samples. We used a custom NGS panel, targeting 34 cancer-related genes, mainly of the BRCA and PARP pathways, and analyzed NGS data to identify somatic and germline variants in Italian patients affected by primary epithelial ovarian cancer. We analyzed 75 epithelial ovarian cancer tissues and identified 54 pathogenic variants and 56 variants of unknown significance. TP53 was characterized by the highest mutational rate, occurring in 55% of tested epithelial ovarian cancers (EOCs). Interestingly, a subset of 8 EOCs showed pathogenic variants of homologous recombination pathway, which could be sensitive to PARP-inhibitor therapies. Germline analysis of actionable genes revealed 4 patients carrier of pathogenic germline variants respectively of RAD51C (2 patients), RAD51D, and PALB2. Molecular profiling of EOCs using our custom NGS panel has enabled the detection of both somatic and germline variants, allowing the selection of patients suitable for targeted therapies, and the identification of high-risk OC families that can benefit from genetic counseling and testing.

卵巢癌(OC)是妇女中第五大常见癌症类型,也是妇女癌症死亡的第四大常见原因。鉴别卵巢癌组织的致病变异对治疗和预防卵巢癌具有重要的临床意义。本研究旨在利用新一代测序(NGS)方法对福尔马林固定石蜡包埋样本的DNA进行分析,评估BRCA1/2生发变异和错配修复缺陷阴性患者队列的突变谱。我们使用定制的NGS面板,针对34个癌症相关基因,主要是BRCA和PARP途径,并分析NGS数据,以确定受原发性上皮性卵巢癌影响的意大利患者的体细胞和种系变异。我们分析了75个上皮性卵巢癌组织,鉴定出54个致病变异和56个意义未知的变异。TP53的特点是突变率最高,发生在55%的上皮性卵巢癌(EOCs)中。有趣的是,8个EOCs子集显示同源重组途径的致病变异,这可能对parp抑制剂治疗敏感。可动基因的种系分析显示,4例患者分别携带RAD51C(2例)、RAD51D和PALB2的致病种系变异。使用我们定制的NGS面板对EOCs进行分子分析,可以检测体细胞和种系变异,从而选择适合靶向治疗的患者,并确定可以从遗传咨询和测试中受益的高危OC家族。
{"title":"Targeted molecular profiling of epithelial ovarian cancer from Italian BRCA wild-type patients with a BRCA and PARP pathways gene panel","authors":"Annamaria Salvati ,&nbsp;Ileana Carnevali ,&nbsp;Elena Alexandrova ,&nbsp;Sofia Facchi ,&nbsp;Susanna Ronchi ,&nbsp;Laura Libera ,&nbsp;Nora Sahnane ,&nbsp;Domenico Memoli ,&nbsp;Jessica Lamberti ,&nbsp;Sonia Amabile ,&nbsp;Stefano Pepe ,&nbsp;Roberta Tarallo ,&nbsp;Fausto Sessa ,&nbsp;Alessandro Weisz ,&nbsp;Maria Grazia Tibiletti ,&nbsp;Francesca Rizzo","doi":"10.1016/j.yexmp.2022.104833","DOIUrl":"10.1016/j.yexmp.2022.104833","url":null,"abstract":"<div><p><span>Ovarian cancer (OC) is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. Identification of pathogenic variants in OC tissues has an important clinical significance for therapeutic and prevention purposes. This study aims to evaluate the mutational profile of a patient cohort, negative for </span><em>BRCA1/2</em><span><span> germinal variants and Mismatch Repair<span> defects, using next-generation sequencing (NGS) approach on DNA<span> from formalin-fixed paraffin-embedded samples. We used a custom NGS panel, targeting 34 cancer-related genes, mainly of the BRCA and PARP pathways, and analyzed NGS data to identify somatic and </span></span></span>germline<span> variants in Italian patients affected by primary epithelial ovarian cancer. We analyzed 75 epithelial ovarian cancer tissues and identified 54 pathogenic variants and 56 variants of unknown significance. </span></span><em>TP53</em><span> was characterized by the highest mutational rate<span>, occurring in 55% of tested epithelial ovarian cancers (EOCs). Interestingly, a subset of 8 EOCs showed pathogenic variants of homologous recombination pathway, which could be sensitive to PARP-inhibitor therapies. Germline analysis of actionable genes revealed 4 patients carrier of pathogenic germline variants respectively of </span></span><span><em>RAD51C</em></span> (2 patients), <em>RAD51D</em>, and <span><em>PALB2</em></span><span><span>. Molecular profiling<span> of EOCs using our custom NGS panel has enabled the detection of both somatic and germline variants, allowing the selection of patients suitable for targeted therapies, and the identification of high-risk OC families that can benefit from </span></span>genetic counseling and testing.</span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104833"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10703384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The impact of MCP1-2518A/G and CCR2-V64I genetic polymorphisms in Egyptian sickle cell disease patients MCP1-2518A/G和CCR2-V64I基因多态性在埃及镰状细胞病患者中的影响
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104834
Nihal Salah Ibrahim , Manal Mohamed Makhlouf , Gehan Hamed Shahin , Mona Kamal Elghamrawy , Nehad Mohammed Hussein

Background

Sickle cell disease (SCD) is an inherited genetic disorders of hemoglobin that causes multisystem morbidity. The pathophysiology of SCD is complex and includes HbS polymerization/sickling, hemolysis, endothelial dysfunction and inflammation. Chemokines are proteins playing an important role in the inflammation process and could be involved the context of pro-inflammatory SCD. Some chemokine polymorphism were found to be associated with clinical complication in SCD.

Aim of the study

Was to explore the frequency and the possible effect of Monocyte Chemo-attractant Protein 1–2518A/G (MCP1–2518A/G) and Chemokine Receptor 2-V64I (CCR2-V64I) genetic polymorphisms on clinical and laboratory disease-related variables in Egyptian Sickle cell disease patients.

Patients and methods

Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group.

Results

The study revealed that the MCP1–2518 polymorphic genotypes (AG & GG) showed no statistically significant difference in the distribution of the polymorphic genotypes between SCD patients and the controls (p = 0.164). While a significantly higher frequency of the mutant variants CCR2-V64I GA/AA among SCD patients than the control subjects were found (p = 0.032). Regarding the clinic-pathological features, the frequency of recurrent infections, vaso-occlusive crisis, severe vaso-occlusive crisis and number of hospitalization/year were higher in patients harbouring the MCP1–2518A/G and CCR2-V64I polymorphic genotypes than the wild genotype, and gall bladder complications were higher in MCP1–2518 G allele patients, whereas surgical splenectomy were higher in CCR2-V64I A allele patients (p < 0.05).

In conclusion

MCP1–2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.

背景镰状细胞病(SCD)是一种遗传性血红蛋白疾病,可引起多系统发病。SCD的病理生理是复杂的,包括HbS聚合/镰状细胞、溶血、内皮功能障碍和炎症。趋化因子是在炎症过程中发挥重要作用的蛋白质,可能与促炎性SCD有关。发现一些趋化因子多态性与SCD的临床并发症有关。目的探讨单核细胞趋化因子蛋白1-2518A /G (MCP1-2518A /G)和趋化因子受体2-V64I (CCR2-V64I)基因多态性在埃及镰状细胞病患者临床和实验室疾病相关变量中的频率及其可能的影响。患者与方法采用PCR-RFLP技术对80例SCD患者和50例健康对照组的2个基因进行分型。结果MCP1-2518多态性基因型(AG &GG)的多态性基因型分布在SCD患者与对照组之间无统计学差异(p = 0.164)。而SCD患者中CCR2-V64I GA/AA的突变频率明显高于对照组(p = 0.032)。在临床病理特征方面,MCP1-2518A /G和CCR2-V64I多态性基因型患者的复发感染频率、血管闭塞危象、严重血管闭塞危象和住院/年次数均高于野生基因型患者,mcp1 - 2518g等位基因患者胆囊并发症发生率较高,而CCR2-V64I等位基因A等位基因患者的脾切除术发生率较高(p <0.05)。结论mcp1 - 2518a /G和CCR2-V64I基因多态性可能影响镰状细胞病的临床严重程度。
{"title":"The impact of MCP1-2518A/G and CCR2-V64I genetic polymorphisms in Egyptian sickle cell disease patients","authors":"Nihal Salah Ibrahim ,&nbsp;Manal Mohamed Makhlouf ,&nbsp;Gehan Hamed Shahin ,&nbsp;Mona Kamal Elghamrawy ,&nbsp;Nehad Mohammed Hussein","doi":"10.1016/j.yexmp.2022.104834","DOIUrl":"10.1016/j.yexmp.2022.104834","url":null,"abstract":"<div><h3>Background</h3><p>Sickle cell disease<span><span> (SCD) is an inherited genetic disorders of hemoglobin that causes multisystem morbidity. The pathophysiology<span> of SCD is complex and includes HbS polymerization/sickling, hemolysis, endothelial dysfunction and inflammation. </span></span>Chemokines are proteins playing an important role in the inflammation process and could be involved the context of pro-inflammatory SCD. Some chemokine polymorphism were found to be associated with clinical complication in SCD.</span></p></div><div><h3>Aim of the study</h3><p>Was to explore the frequency and the possible effect of Monocyte<span> Chemo-attractant Protein 1–2518A/G (MCP1–2518A/G) and Chemokine Receptor<span> 2-V64I (CCR2-V64I) genetic polymorphisms on clinical and laboratory disease-related variables in Egyptian Sickle cell disease patients.</span></span></p></div><div><h3>Patients and methods</h3><p>Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group.</p></div><div><h3>Results</h3><p>The study revealed that the MCP1–2518 polymorphic genotypes (AG &amp; GG) showed no statistically significant difference in the distribution of the polymorphic genotypes between SCD patients and the controls (<em>p</em> = 0.164). While a significantly higher frequency of the mutant variants CCR2-V64I GA/AA among SCD patients than the control subjects were found (<em>p</em><span><span> = 0.032). Regarding the clinic-pathological features, the frequency of recurrent infections, vaso-occlusive crisis, severe vaso-occlusive crisis and number of hospitalization/year were higher </span>in patients<span> harbouring the MCP1–2518A/G and CCR2-V64I polymorphic genotypes than the wild genotype, and gall bladder<span> complications were higher in MCP1–2518 G allele patients, whereas surgical splenectomy were higher in CCR2-V64I A allele patients (</span></span></span><em>p</em> &lt; 0.05).</p></div><div><h3>In conclusion</h3><p>MCP1–2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104834"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer Circ0001955介导的调控通路在结直肠癌中的重要性
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104819
Sepideh Kadkhoda , Soudeh Ghafouri-Fard , Farshid Noorbakhsh , Sima Ravaei , Farzaneh Darbeheshti , Mahsa M. Amoli , Reza Taslimi , Abbas Shakoori

Introduction

Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC.

Methods

After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed.

Results

Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters.

Conclusion

Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.

结直肠癌(colorectal cancer, CRC)是近年来最常见的癌症之一。鉴于非编码rna最近在包括癌症在内的各种疾病中获得的重要性,我们决定设计这项研究来评估circ0001955/miR-145-5p/ONECUT2轴在CRC中的表达水平。方法在对与CRC相关的GEO数据集进行生物信息学分析后,假设存在circ0001955/ miR-145-5p/ ONECUT2通路。然后,采用qRT- PCR方法检测这些基因在50例结直肠癌样本及其邻近组织中的表达水平。分析相关系数、受试者工作特征(ROC)曲线及circ0001955水平与患者临床病理参数的相关性。结果scirc0001955和ONECUT2显著上调,而miR-145-5p在结直肠癌样本中的表达水平较邻近组织降低(p <0.05)。此外,在circ0001955、miR-145-5p和ONECUT2的表达水平之间观察到具有统计学意义的相关性。我们没有发现circ0001955的表达与临床病理参数之间有任何显著的相关性。结论本研究表明circ0001955在结直肠癌中表达异常。这一发现为研究人员更好地了解CRC发病机制的潜在途径,从而找到新的治疗途径打开了一扇新的窗口。
{"title":"The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer","authors":"Sepideh Kadkhoda ,&nbsp;Soudeh Ghafouri-Fard ,&nbsp;Farshid Noorbakhsh ,&nbsp;Sima Ravaei ,&nbsp;Farzaneh Darbeheshti ,&nbsp;Mahsa M. Amoli ,&nbsp;Reza Taslimi ,&nbsp;Abbas Shakoori","doi":"10.1016/j.yexmp.2022.104819","DOIUrl":"10.1016/j.yexmp.2022.104819","url":null,"abstract":"<div><h3>Introduction</h3><p>Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC.</p></div><div><h3>Methods</h3><p>After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed.</p></div><div><h3>Results</h3><p>Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (<em>p</em> &lt; 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters.</p></div><div><h3>Conclusion</h3><p>Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104819"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10335816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single nucleotide polymorphism patterns associated with a cancer resistant phenotype 与癌症耐药性表型相关的单核苷酸多态性模式。
IF 3.6 4区 医学 Q2 PATHOLOGY Pub Date : 2022-10-01 DOI: 10.1016/j.yexmp.2022.104812
June K. Dunnick , Arun R. Pandiri , Keith R. Shockley , Ronald Herbert , Deepak Mav , Dhiral Phadke , Ruchir R. Shah , B. Alex Merrick

Background and aims

In this study ten mouse strains representing ~90% of genetic diversity in laboratory mice (B6C3F1/J, C57BL/6J, C3H/HeJ, A/J, NOD.B1oSnH2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ) were examined to identify the mouse strain with the lowest incidence of cancer. The unique single polymorphisms (SNPs) associated with this low cancer incidence are reported.

Methods

Evaluations of cancer incidence in the 10 mouse strains were based on gross and microscopic diagnosis of tumors. Single nucleotide polymorphisms (SNPs) in the coding regions of the genome were derived from the respective mouse strains located in the Sanger mouse sequencing database and the B6C3F1/N genome from the National Toxicology Program (NTP).

Results

The WSB strain had an overall lower incidence of both benign and malignant tumors compared to the other mouse strains. At 2 years, the incidence of total malignant tumors (Poly-3 incidence rate) ranged from 2% (WSB) to 92% (C3H) in males, and 14% (WSB) to 93% (NZO) in females, and the total incidence of benign and malignant tumor incidence ranged from 13% (WSB) to 99% (C3H) in males and 25% (WSB) to 96% (NOD) in females. Single nucleotide polymorphism (SNP) patterns were examined in the following strains: B6C3F1/N, C57BL/6J, C3H/HeJ, 129S1/SvImJ, A/J, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. We identified 7519 SNPs (involving 5751 Ensembl transcripts of 3453 Ensembl Genes) that resulted in a unique amino acid change in the coding region of the WSB strain.

Conclusions

The inherited genetic patterns in the WSB cancer-resistant mouse strain occurred in genes involved in multiple cell functions including mitochondria, metabolic, immune, and membrane-related cell functions. The unique SNP patterns in a cancer resistant mouse strain provides insights for understanding and developing strategies for cancer prevention.

背景和目的:本研究检测了10种代表实验室小鼠遗传多样性约90%的小鼠品系(B6C3F1/J、C57BL/6J、C3H/HeJ、A/J、NOD.B1oSnH2/J、NZO/HILtJ、129S1/SvImJ、WSB/EiJ、PWK/PhJ、CAST/EiJ),以确定癌症发病率最低的小鼠品。报道了与这种低癌症发病率相关的独特的单一多态性(SNPs)。方法:根据肿瘤的大体和显微镜诊断,对10株小鼠癌症发病率进行评价。基因组编码区的单核苷酸多态性(SNPs)来源于桑格小鼠测序数据库中的相应小鼠株和国家毒理学计划(NTP)中的B6C3F1/N基因组。结果:与其他小鼠株相比,WSB株的良性和恶性肿瘤发生率总体较低。2年时,男性的总恶性肿瘤发病率(Poly-3发病率)为2%(WSB)至92%(C3H),女性为14%(WSB和93%(NZO),男性的良性和恶性肿瘤总发病率为13%(WSB到99%(C3H,女性为25%(WSB至96%(NOD))。在以下菌株中检测了单核苷酸多态性(SNP)模式:B6C3F1/N、C57BL/6J、C3H/HeJ、129S1/SvImJ、A/J、NZO/HILtJ、CAST/EiJ、PWK/PhJ和WSB/EiJ。我们鉴定了7519个SNPs(涉及3453个Ensembl基因的5751个Ensemble转录本),这些SNPs导致WSB菌株编码区发生独特的氨基酸变化。结论:WSB抗癌小鼠株的遗传模式发生在涉及多种细胞功能的基因中,包括线粒体、代谢、免疫和膜相关细胞功能。癌症抗性小鼠品系中独特的SNP模式为理解和开发癌症预防策略提供了见解。
{"title":"Single nucleotide polymorphism patterns associated with a cancer resistant phenotype","authors":"June K. Dunnick ,&nbsp;Arun R. Pandiri ,&nbsp;Keith R. Shockley ,&nbsp;Ronald Herbert ,&nbsp;Deepak Mav ,&nbsp;Dhiral Phadke ,&nbsp;Ruchir R. Shah ,&nbsp;B. Alex Merrick","doi":"10.1016/j.yexmp.2022.104812","DOIUrl":"10.1016/j.yexmp.2022.104812","url":null,"abstract":"<div><h3>Background and aims</h3><p>In this study ten mouse strains representing ~90% of genetic diversity in laboratory mice (B6C3F1/J, C57BL/6J, C3H/HeJ, A/J, NOD.B1oSnH2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ) were examined to identify the mouse strain with the lowest incidence of cancer. The unique single polymorphisms (SNPs) associated with this low cancer incidence are reported.</p></div><div><h3>Methods</h3><p>Evaluations of cancer incidence in the 10 mouse strains were based on gross and microscopic diagnosis of tumors. Single nucleotide polymorphisms (SNPs) in the coding regions of the genome were derived from the respective mouse strains located in the Sanger mouse sequencing database and the B6C3F1/N genome from the National Toxicology Program (NTP).</p></div><div><h3>Results</h3><p>The WSB strain had an overall lower incidence of both benign and malignant tumors compared to the other mouse strains. At 2 years, the incidence of total malignant tumors (Poly-3 incidence rate) ranged from 2% (WSB) to 92% (C3H) in males, and 14% (WSB) to 93% (NZO) in females, and the total incidence of benign and malignant tumor incidence ranged from 13% (WSB) to 99% (C3H) in males and 25% (WSB) to 96% (NOD) in females. Single nucleotide polymorphism (SNP) patterns were examined in the following strains: B6C3F1/N, C57BL/6J, C3H/HeJ, 129S1/SvImJ, A/J, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. We identified 7519 SNPs (involving 5751 Ensembl transcripts of 3453 Ensembl Genes) that resulted in a unique amino acid change in the coding region of the WSB strain.</p></div><div><h3>Conclusions</h3><p>The inherited genetic patterns in the WSB cancer-resistant mouse strain occurred in genes involved in multiple cell functions including mitochondria, metabolic, immune, and membrane-related cell functions. The unique SNP patterns in a cancer resistant mouse strain provides insights for understanding and developing strategies for cancer prevention.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104812"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Experimental and molecular pathology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1