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A Novel Pair of Compound Heterozygous Mutation of EYS in a Han Chinese Family with Retinitis Pigmentosa. 中国汉族色素性视网膜炎家族EYS的一对新的复合杂合突变。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-08-01 DOI: 10.1089/gtmb.2023.0016
Chao Dai, Weiming Ren, Yao Wei, Chunbao Xie, Suyang Duan, Qi Li, Lingxi Jiang, Yi Shi

Background: Retinitis pigmentosa (RP) is a complex inherited and progressive degenerative retinal disease. The eyes shut homolog (EYS) is frequently associated with RP is surprisingly high. Exploring the function of EYS is quite difficult due to the unique gene size and species specificity. Gene therapy may provide a breakthrough to treat this disease. Therefore, exploring and clarifying pathogenic mutations of EYS-associated RP has important guiding significance for clinical treatment. Methods: Clinical and molecular genetic data for EYS-associated RP were retrospectively analyzed. Sanger sequencing was applied to identify novel mutations in these patients. Candidate pathogenic variants were subsequently evaluated using bioinformatic tools. Results: A novel pair of compound heterozygous mutations was identified: a novel stop-gain mutation c.2439C>A (p.C813fsX) and a frameshift deletion mutation c.6714delT (p. P2238fsX) of the EYS gene in the RP family. Both of these mutations were rare or absent in the 1000 Genomes Project, dbSNP, and Genome Aggregation Database (gnomAD). These two mutations would result in a lack of multiple functionally important epidermal growth factor-like and Laminin G-like coding regions in EYS. Conclusions: A novel compound heterozygote of the EYS gene in a Chinese family with an autosomal inheritance pattern of RP was identified. Identifying more pathogenic mutations and expanding the mutation spectrum of the EYS gene will contribute to a more comprehensive understanding of the molecular pathogenesis of RP disease that could be gained in the future. It also could provide an important basis for the diagnosis, clinical management, and genetic counseling of the disease.

背景:视网膜色素变性(RP)是一种复杂的遗传性进行性退行性视网膜疾病。闭眼同源基因(eyes shut homolog, EYS)通常与RP相关,且RP高得惊人。由于其独特的基因大小和物种特异性,研究EYS的功能相当困难。基因疗法可能是治疗这种疾病的突破口。因此,探索和阐明eys相关RP的致病突变对临床治疗具有重要的指导意义。方法:回顾性分析眼相关性RP的临床及分子遗传学资料。Sanger测序用于鉴定这些患者的新突变。候选致病变异随后使用生物信息学工具进行评估。结果:在RP家族EYS基因中发现了一对新的复合杂合突变:一个新的停止增益突变c.2439C>A (p. c813fsx)和一个移码缺失突变c.6714delT (p. P2238fsX)。这两种突变在1000基因组计划、dbSNP和基因组聚集数据库(gnomAD)中都是罕见或不存在的。这两个突变将导致EYS中缺乏多个功能重要的表皮生长因子样和层粘连蛋白g样编码区。结论:在一个RP常染色体遗传的中国家庭中发现了一个新的EYS基因复合杂合子。发现更多的致病突变,扩大EYS基因的突变谱,将有助于在未来更全面地了解RP病的分子发病机制。为该病的诊断、临床管理和遗传咨询提供重要依据。
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引用次数: 0
LINC00891 Attenuates the Proliferation and Metastasis of Osteosarcoma Cells via miR-27a-3p/TET1 Axis. LINC00891通过miR-27a-3p/TET1轴减弱骨肉瘤细胞的增殖和转移。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-08-01 DOI: 10.1089/gtmb.2023.0163
Shufang Zhang, Rongchun Chen

Objective: There is currently no adequate treatment for osteosarcoma, a bone malignancy that poses a serious threat to adolescents and children. The dysregulation of long noncoding RNAs is associated with many cancers, including osteosarcoma. LINC00891 expression is aberrant in endometrial cancer, lung cancer, and thyroid cancer, and likely regulate the malignant behavior of cancer. However, the potential function and mechanisms of LINC00891 in osteosarcoma progression remain unclear. Materials and Methods: LINC00891, miR-27a-3p, and TET1 mRNA expression in osteosarcoma cells were analyzed using quantitative reverse transcription-polymerase chain reaction. CCK-8 and Transwell experiments were performed on osteosarcoma cells to investigate proliferation, migration, and invasion, respectively. Ten-eleven translocation 1 (TET1) protein was analyzed using western blotting. Luciferase experiment was performed to investigate the interactions between LINC00891 with miR-27a-3p, and miR-27a-3p with TET1. Results: LINC00891 expression was dramatically decreased in the five osteosarcoma cell lines examined, particularly in 143B and SaoS-2 cells. LINC00891 overexpression due to plasmid transfection sharply blocked the proliferation, migration, and invasion of osteosarcoma cells. Dual-luciferase reporter experiments found that LINC00891 sponges miR-27a-3p, and LINC00891 overexpression sharply decreases miR-27a-3p expression. Transfection with miR-27a-3p mimic accelerated the malignant behaviors in LINC00891 overexpressed-osteosarcoma cells. Moreover, TET1 was a novel targeted-gene of miR-27a-3p. TET1 protein was significantly impeded, whereas LINC00891 overexpression elevated TET1 mRNA and protein in osteosarcoma cells. MiR-27a-3p overexpression inhibited TET1 mRNA and protein in osteosarcoma cells. Conclusions: Our study verified that LINC00891 attenuates the proliferation and metastasis of osteosarcoma cells via the miR-27a-3p/TET1 axis. This study clarifies a new mechanism and therapeutic target for the development of osteosarcoma.

目的:骨肉瘤是一种严重威胁青少年和儿童的骨恶性肿瘤,目前尚无足够的治疗方法。长链非编码rna的失调与许多癌症有关,包括骨肉瘤。LINC00891在子宫内膜癌、肺癌和甲状腺癌中表达异常,可能调控肿瘤的恶性行为。然而,LINC00891在骨肉瘤进展中的潜在功能和机制尚不清楚。材料与方法:采用定量逆转录-聚合酶链反应分析骨肉瘤细胞中LINC00891、miR-27a-3p和TET1 mRNA的表达。CCK-8和Transwell实验分别对骨肉瘤细胞进行增殖、迁移和侵袭实验。western blotting检测10 - 11易位1 (TET1)蛋白。我们通过荧光素酶实验来研究LINC00891与miR-27a-3p以及miR-27a-3p与TET1的相互作用。结果:LINC00891在5种骨肉瘤细胞系中表达显著降低,尤其是在143B和SaoS-2细胞中。质粒转染后LINC00891过表达可明显阻断骨肉瘤细胞的增殖、迁移和侵袭。双荧光素酶报告基因实验发现,LINC00891抑制miR-27a-3p,过表达LINC00891可显著降低miR-27a-3p的表达。转染miR-27a-3p模拟物加速了LINC00891过表达骨肉瘤细胞的恶性行为。此外,TET1是miR-27a-3p的一个新的靶向基因。骨肉瘤细胞中TET1蛋白表达明显受阻,而LINC00891过表达升高TET1 mRNA和蛋白表达。MiR-27a-3p过表达抑制骨肉瘤细胞TET1 mRNA和蛋白表达。结论:我们的研究证实了LINC00891通过miR-27a-3p/TET1轴减弱骨肉瘤细胞的增殖和转移。本研究为骨肉瘤的发生提供了新的机制和治疗靶点。
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引用次数: 0
Diagnose Quickly and Effectively: Now. 快速有效地诊断:现在。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-08-01 DOI: 10.1089/gtmb.2023.29075.persp
Dawn Barry, Sharon F Terry
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引用次数: 0
Association of RAD51, XRCC1, XRCC2, and XRCC3 Polymorphisms with Risk of Breast Cancer. RAD51、XRCC1、XRCC2和XRCC3多态性与乳腺癌风险的关系
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-07-01 DOI: 10.1089/gtmb.2023.0012
Priyanka Gupta, Vasudha Sambyal, Kamlesh Guleria, Manjit Singh Uppal, Meena Sudan

Background: DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, RAD51 rs1801320, XRCC1 rs25487, XRCC2 rs3218536, and XRCC3 rs861539 with the risk of breast cancer. Materials and Methods: In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. Results: The GC genotype (p = 0.018) and the combined GC+CC (p = 0.03) genotypes of RAD51 rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype (p = 0.0001), the combined CT+TT genotypes (p = 0.0002), and the T allele (p = 0.0019) of XRCC3 rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of XRCC1 rs25487 and XRCC2 rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between XRCC3 and XRCC2. String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. Conclusion: RAD51 rs1801320 and XRCC3 rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among XRCC1, XRCC2, XRCC3, and RAD51.

背景:DNA修复基因是与乳腺癌相关的低外显子基因之一。然而,DNA修复基因的变异可能改变其蛋白质功能,从而导致致癌。乳腺癌是印度女性中最常见的癌症。本研究的目的是确定RAD51 rs1801320、XRCC1 rs25487、XRCC2 rs3218536和XRCC3 rs861539四个参与DNA修复途径的基因的单核苷酸多态性(SNP)与乳腺癌风险的关联,如果存在关联的话。材料与方法:采用聚合酶链反应-限制性片段长度多态性分析对611名女性受试者(311名乳腺癌患者和300名健康对照)进行4种snp的筛选。采用多因素降维分析(MDR)估计基因-基因相互作用。利用STRING数据库进行蛋白-蛋白互作网络分析。结果:RAD51 rs1801320的GC基因型(p = 0.018)和GC+CC联合基因型(p = 0.03)与乳腺癌风险降低显著相关。CT基因型(p = 0.0001)、CT+TT联合基因型(p = 0.0002)和XRCC3 rs861539多态性的T等位基因(p = 0.0019)与乳腺癌风险降低相关。未发现XRCC1 rs25487和XRCC2 rs3218536多态性与乳腺癌相关。MDR分析显示XRCC3和XRCC2之间存在正互作。字符串网络分析显示,RAD51、XRCC1、XRCC2和XRCC3蛋白与其他乳腺癌相关蛋白如BRCA2之间存在强相互作用。结论:RAD51 rs1801320和XRCC3 rs861539多态性与乳腺癌风险降低相关。有证据表明,XRCC1、XRCC2、XRCC3和RAD51之间存在正相互作用。
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引用次数: 0
Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas. 唐氏综合征患儿的中耳炎与鼻咽部和中耳微生物群的变化有关。
IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Pub Date : 2023-07-01 DOI: 10.1089/gtmb.2023.0132
Christina L Elling, Salina H Goff, Scott D Hirsch, Kaitlyn Tholen, Jennifer M Kofonow, Danielle Curtis, Charles E Robertson, Jeremy D Prager, Patricia J Yoon, Todd M Wine, Kenny H Chan, Melissa A Scholes, Norman R Friedman, Daniel N Frank, Brian W Herrmann, Regie Lyn P Santos-Cortez

Background: Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. Method: We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (n = 11) compared with those without DS (n = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. Results: Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. Conclusion: Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.

背景:中耳炎(OM)是指通常由感染引起的中耳(ME)炎症。在全球范围内,中耳炎是导致听力损失的主要原因,也是幼儿最常诊断出的疾病。就中耳炎而言,患有唐氏综合征(DS)的儿童患者发病率更高、病情更严重、治疗效果更差。然而,迄今为止,还没有研究对患有唐氏综合征和 OM 的儿童的细菌谱进行调查。方法:我们的目的是确定患有 DS 的小儿 OM 患者(n = 11)与不患有 DS 的小儿 OM 患者(n = 84)相比,其 ME 和鼻咽 (NP) 微生物群中的细菌谱组成或单个类群的相对丰度是否存在差异。我们对 16S rRNA 基因进行了测序,并分析了序列数据的多样性指数和各个类群的相对丰度。结果显示DS 患儿的 ME 和 NP 微生物群的生物多样性有所增加。在 OM 患儿中,DS 与 ME 中生物多样性增加和特定类群相对丰度较高有关。结论:我们的研究结果表明,与对照组相比,DS 儿童 NP 中的菌群失调是导致他们更易患 OM 的原因之一。这些研究结果表明,DS会影响粘膜微生物群的调节,并导致OM病理变化。
{"title":"Otitis Media in Children with Down Syndrome Is Associated with Shifts in the Nasopharyngeal and Middle Ear Microbiotas.","authors":"Christina L Elling, Salina H Goff, Scott D Hirsch, Kaitlyn Tholen, Jennifer M Kofonow, Danielle Curtis, Charles E Robertson, Jeremy D Prager, Patricia J Yoon, Todd M Wine, Kenny H Chan, Melissa A Scholes, Norman R Friedman, Daniel N Frank, Brian W Herrmann, Regie Lyn P Santos-Cortez","doi":"10.1089/gtmb.2023.0132","DOIUrl":"10.1089/gtmb.2023.0132","url":null,"abstract":"<p><p><b><i>Background:</i></b> Otitis media (OM) is defined as middle ear (ME) inflammation that is usually due to infection. Globally, OM is a leading cause of hearing loss and is the most frequently diagnosed disease in young children. For OM, pediatric patients with Down syndrome (DS) demonstrate higher incidence rates, greater severity, and poorer outcomes. However, to date, no studies have investigated the bacterial profiles of children with DS and OM. <b><i>Method:</i></b> We aimed to determine if there are differences in composition of bacterial profiles or the relative abundance of individual taxa within the ME and nasopharyngeal (NP) microbiotas of pediatric OM patients with DS (<i>n</i> = 11) compared with those without DS (<i>n</i> = 84). We sequenced the 16S rRNA genes and analyzed the sequence data for diversity indices and relative abundance of individual taxa. <b><i>Results:</i></b> Individuals with DS demonstrated increased biodiversity in their ME and NP microbiotas. In children with OM, DS was associated with increased biodiversity and higher relative abundance of specific taxa in the ME. <b><i>Conclusion:</i></b> Our findings suggest that dysbioses in the NP of DS children contributes to their increased susceptibility to OM compared with controls. These findings suggest that DS influences regulation of the mucosal microbiota and contributes to OM pathology.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluating the Clinical Application of Automatic Chromosome Harvesting for Prenatal Karyotype Analysis. 染色体自动采集在产前核型分析中的临床应用评价。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-07-01 DOI: 10.1089/gtmb.2023.0047
Yunmeng Wang, Yifan Feng, Chanchan Ma, Jing Zhao, Shiying Sun

Objective: The clinical value of an automatic chromosome harvester was evaluated, which included a comparison between the manual and automatic harvesting for the isolation of amniotic fluid cell chromosomes. Methods: Amniotic fluid samples from 96 high-risk gravida cases identified at 17-25 weeks treated at the Prenatal Diagnostic and Reproductive Center from June to July 2022 were collected. These samples underwent both manual and automatic chromosome collection, and their harvest time and number of amniotic cells were compared. These chromosomes were then used to produce karyotypic data for each sample using an automatic chromosomal karyotype analysis system, scan karyotype. Results: The average automatic harvesting time per sample, 3.92 min, was significantly lower than that of the manual harvesting, 7.89 min (p < 0.001). In addition, the average number of cells from the automatic harvesting (4.16 × 106 pieces) was significantly increased when compared with those of the manual group (2.10 × 106 pieces; p < 0.001). Further karyotyping revealed that both sets of chromosomes produced clear bands and good dispersion data, producing no significant differences in these evaluations (p > 0.05). However, the number of analyzable karyotypes obtained using the automatic harvester was significantly higher than those of the manual harvesting (p < 0.001). Conclusions: The automatic chromosome harvester can effectively save time, manual labor and consumables, harvest more analyzable karyotypes, and improve the efficiency of clinical diagnosis. The automatic chromosome harvester is highly stable and repeatable, which has the potential to help achieve large-scale standardized chromosome harvesting and is worthy of widespread clinical promotion.

目的:评价自动染色体采集器在羊水细胞染色体分离中的临床应用价值。方法:收集2022年6月至7月在产前诊断和生殖中心接受治疗的17至25周的96例高危孕妇的羊水样本。这些样本进行了手动和自动染色体采集,并对采集时间和羊水细胞数量进行了比较。然后使用自动染色体核型分析系统扫描核型,将这些染色体用于产生每个样本的核型数据。结果:每个样本的平均自动采集时间为3.92 min,显著低于人工收割的7.89 最小值(p 6件)与手动组(2.10 × 106件;p p > 0.05)。然而,使用自动收获机获得的可分析核型的数量显著高于手动收获机(p 结论:全自动染色体采集机可以有效地节省时间、人工和耗材,采集更多的可分析核型,提高临床诊断效率。自动染色体收获器具有高度稳定性和可重复性,有助于实现大规模标准化染色体收获的潜力,值得临床广泛推广。
{"title":"Evaluating the Clinical Application of Automatic Chromosome Harvesting for Prenatal Karyotype Analysis.","authors":"Yunmeng Wang,&nbsp;Yifan Feng,&nbsp;Chanchan Ma,&nbsp;Jing Zhao,&nbsp;Shiying Sun","doi":"10.1089/gtmb.2023.0047","DOIUrl":"10.1089/gtmb.2023.0047","url":null,"abstract":"<p><p><b><i>Objective:</i></b> The clinical value of an automatic chromosome harvester was evaluated, which included a comparison between the manual and automatic harvesting for the isolation of amniotic fluid cell chromosomes. <b><i>Methods:</i></b> Amniotic fluid samples from 96 high-risk gravida cases identified at 17-25 weeks treated at the Prenatal Diagnostic and Reproductive Center from June to July 2022 were collected. These samples underwent both manual and automatic chromosome collection, and their harvest time and number of amniotic cells were compared. These chromosomes were then used to produce karyotypic data for each sample using an automatic chromosomal karyotype analysis system, scan karyotype. <b><i>Results:</i></b> The average automatic harvesting time per sample, 3.92 min, was significantly lower than that of the manual harvesting, 7.89 min (<i>p</i> < 0.001). In addition, the average number of cells from the automatic harvesting (4.16 × 10<sup>6</sup> pieces) was significantly increased when compared with those of the manual group (2.10 × 10<sup>6</sup> pieces; <i>p</i> < 0.001). Further karyotyping revealed that both sets of chromosomes produced clear bands and good dispersion data, producing no significant differences in these evaluations (<i>p</i> > 0.05). However, the number of analyzable karyotypes obtained using the automatic harvester was significantly higher than those of the manual harvesting (<i>p</i> < 0.001). <b><i>Conclusions:</i></b> The automatic chromosome harvester can effectively save time, manual labor and consumables, harvest more analyzable karyotypes, and improve the efficiency of clinical diagnosis. The automatic chromosome harvester is highly stable and repeatable, which has the potential to help achieve large-scale standardized chromosome harvesting and is worthy of widespread clinical promotion.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Application of Artificial Intelligence in the Diagnosis of Cancer and Rare Genetic Diseases. 人工智能在癌症和罕见遗传病诊断中的应用。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-07-01 DOI: 10.1089/gtmb.2023.29074.persp
Danielle Donadio, Sharon F Terry
{"title":"The Application of Artificial Intelligence in the Diagnosis of Cancer and Rare Genetic Diseases.","authors":"Danielle Donadio,&nbsp;Sharon F Terry","doi":"10.1089/gtmb.2023.29074.persp","DOIUrl":"https://doi.org/10.1089/gtmb.2023.29074.persp","url":null,"abstract":"","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Role of Genetic Polymorphism and Expression of Angiopoietin-2 in Patients with Primary Liver Cancer Among the Southeastern Chinese Hans Population. 血管生成素-2基因多态性和表达在中国东南汉族原发性肝癌患者中的作用
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-06-01 DOI: 10.1089/gtmb.2022.0198
Bin Wang, Yunxiao Lv, Shenjian Ye, Jin Zhao, Xinling Pan

Background: Angiopoietin-2 (Ang2)-mediated angiogenesis plays a crucial role in the pathogenesis of vascular-rich cancers. However, the genetic polymorphism and expression level of Ang2 in patients with primary liver cancer remain unknown. Methods: This study included 234 primary liver cancer patients and 199 healthy controls. The expression levels of Ang2 in liver cancer tissues and plasma were determined. Peripheral blood samples were collected to test five ANGPT2 single nucleotide polymorphisms (rs2442598, rs734701, rs1823375, rs11137037, and rs12674822). Results: Plasma Ang2 levels in patients with liver cancer were upregulated compared with that in healthy controls. The upregulation of plasma Ang2 levels was significantly associated with vascular invasion, metastasis, and clinical stage. Notably, the transcription level of ANGPT2 was elevated in tumor tissues compared with para-carcinoma tissues. Individuals with the TT genotype at rs2442598 and genotype AC and AC+CC at rs11137037 had higher liver cancer risk compared with healthy controls. Conclusions: Upregulated Ang2 levels in blood plasma and cancer tissues of liver cancer patients confirm that Ang2 plays a vital role in the pathogenesis of liver cancer. ANGPT2 rs2442588 and rs11137037 are associated with liver cancer risk, thereby highlighting their role in screening individuals susceptible to liver cancer.

背景:血管生成素-2 (Ang2)介导的血管生成在血管丰富的癌症的发病机制中起着至关重要的作用。然而,原发性肝癌患者中Ang2的基因多态性和表达水平尚不清楚。方法:本研究纳入234例原发性肝癌患者和199例健康对照。测定肝癌组织和血浆中Ang2的表达水平。采集外周血样本检测5个ANGPT2单核苷酸多态性(rs2442598、rs734701、rs1823375、rs11137037和rs12674822)。结果:肝癌患者血浆Ang2水平明显高于正常对照组。血浆Ang2水平上调与血管侵袭、转移及临床分期有显著相关性。值得注意的是,与癌旁组织相比,肿瘤组织中ANGPT2的转录水平升高。与健康对照相比,TT基因型rs2442598和基因型AC和AC+CC rs11137037的个体患肝癌的风险更高。结论:肝癌患者血浆及癌组织中Ang2水平上调,证实了Ang2在肝癌发病过程中起着至关重要的作用。ANGPT2 rs2442588和rs11137037与肝癌风险相关,从而突出了其在筛查肝癌易感个体中的作用。
{"title":"Role of Genetic Polymorphism and Expression of Angiopoietin-2 in Patients with Primary Liver Cancer Among the Southeastern Chinese Hans Population.","authors":"Bin Wang,&nbsp;Yunxiao Lv,&nbsp;Shenjian Ye,&nbsp;Jin Zhao,&nbsp;Xinling Pan","doi":"10.1089/gtmb.2022.0198","DOIUrl":"https://doi.org/10.1089/gtmb.2022.0198","url":null,"abstract":"<p><p><b><i>Background:</i></b> Angiopoietin-2 <b>(</b>Ang2)-mediated angiogenesis plays a crucial role in the pathogenesis of vascular-rich cancers. However, the genetic polymorphism and expression level of Ang2 in patients with primary liver cancer remain unknown. <b><i>Methods:</i></b> This study included 234 primary liver cancer patients and 199 healthy controls. The expression levels of Ang2 in liver cancer tissues and plasma were determined. Peripheral blood samples were collected to test five <i>ANGPT2</i> single nucleotide polymorphisms (rs2442598, rs734701, rs1823375, rs11137037, and rs12674822). <b><i>Results:</i></b> Plasma Ang2 levels in patients with liver cancer were upregulated compared with that in healthy controls. The upregulation of plasma Ang2 levels was significantly associated with vascular invasion, metastasis, and clinical stage. Notably, the transcription level of <i>ANGPT2</i> was elevated in tumor tissues compared with para-carcinoma tissues. Individuals with the TT genotype at rs2442598 and genotype AC and AC+CC at rs11137037 had higher liver cancer risk compared with healthy controls. <b><i>Conclusions:</i></b> Upregulated Ang2 levels in blood plasma and cancer tissues of liver cancer patients confirm that Ang2 plays a vital role in the pathogenesis of liver cancer. <i>ANGPT2</i> rs2442588 and rs11137037 are associated with liver cancer risk, thereby highlighting their role in screening individuals susceptible to liver cancer.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of PIWIL1 Single Nucleotide Polymorphisms on Gastric Cancer Risk in a Chinese Population. PIWIL1单核苷酸多态性对中国人群胃癌风险的影响
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-06-01 DOI: 10.1089/gtmb.2022.0061
Dan Hu, Laicheng Wang, Xin Chen, Yunchai Lin, Shunpeng Zhang, Zongcheng Fan, Feng Peng

Background: PIWI-like proteins contribute to the onset and progression of carcinogenesis. Whether single nucleotide polymorphisms (SNPs) in the PIWI-like 1 (PIWIL1) gene affect the morbidity and mortality of gastric cancer (GC) remains unclear. To investigate the efficacy of PIWIL1 SNPs genotype on the morbidity and mortality of GC and its interaction within PIWIL1 gene SNPs variation and between elevated plasma glucose. Materials and Methods: We conducted a case-control study that contained 216 GC patients and 204 cancer-free controls to compare differential expression of PIWIL1 SNPs. Results: PIWIL1 gene rs1106042 AA and AG genotypes were associated with significantly reduced GC risk (odds ratio [OR]: 0.15 and 0.26, p < 0.001 and p = 0.016), and rs10773771 CT+CC type significantly increased cancer risk (OR: 1.54 p = 0.037). We observed strong associations between rs10773771 and pathological type (p = 0.012), rs11703684, and invasion depth (p = 0.012). We noticed significant gene-gene interaction between rs1106042 and rs10773771 (p = 0.0107). Interaction between the copresence of rs1106042 GG plus hyperglycemia was also significant (relative excess risk due to interaction: 28.78, attributable proportion due to interaction: 68.2%, synergy index: 3.32). Patients with rs1892723 TT and rs1892722 GG+GA type had better survival (p = 0.030 and p = 0.048). Conclusion: rs10773771 CT+CC was associated with GC risk increase, rs1106042 AA and AG function as a protective factor. rs1892723 CT+TT and rs1892722 AA type may portend a poor prognosis. Elevated fasting plasma glucose will significantly increase the risk of PIWIL gene rs1106042 GG carcinogenesis by multiplicative interaction.

背景:piwi样蛋白参与癌变的发生和进展。PIWI-like 1 (PIWIL1)基因的单核苷酸多态性(snp)是否影响胃癌(GC)的发病率和死亡率尚不清楚。目的探讨PIWIL1 snp基因型对胃癌发病率和死亡率的影响及其与PIWIL1基因内snp变异和血糖升高之间的相互作用。材料和方法:我们进行了一项病例对照研究,包括216例胃癌患者和204例无癌对照,比较PIWIL1 snp的差异表达。结果:PIWIL1基因rs1106042 AA和AG基因型与胃癌风险显著降低相关(比值比[OR]: 0.15和0.26,p p = 0.016), rs10773771 CT+CC基因型与胃癌风险显著升高相关(OR: 1.54 p = 0.037)。我们观察到rs10773771与病理类型(p = 0.012)、rs11703684与侵袭深度(p = 0.012)有很强的相关性。我们发现rs1106042和rs10773771之间存在显著的基因-基因互作(p = 0.0107)。rs1106042 GG的存在与高血糖之间的相互作用也很显著(相互作用的相对超额风险:28.78,相互作用的归因比例:68.2%,协同指数:3.32)。rs1892723 TT和rs1892722 GG+GA型患者生存率更高(p = 0.030和p = 0.048)。结论:rs10773771 CT+CC与胃癌风险增加相关,rs1106042 AA和AG为保护因素。rs1892723 CT+TT和rs1892722 AA型可能预示预后不良。空腹血糖升高会通过增殖相互作用显著增加PIWIL基因rs1106042 GG致癌的风险。
{"title":"Impact of PIWIL1 Single Nucleotide Polymorphisms on Gastric Cancer Risk in a Chinese Population.","authors":"Dan Hu,&nbsp;Laicheng Wang,&nbsp;Xin Chen,&nbsp;Yunchai Lin,&nbsp;Shunpeng Zhang,&nbsp;Zongcheng Fan,&nbsp;Feng Peng","doi":"10.1089/gtmb.2022.0061","DOIUrl":"https://doi.org/10.1089/gtmb.2022.0061","url":null,"abstract":"<p><p><b><i>Background:</i></b> PIWI-like proteins contribute to the onset and progression of carcinogenesis. Whether single nucleotide polymorphisms (SNPs) in the PIWI-like 1 (PIWIL1) gene affect the morbidity and mortality of gastric cancer (GC) remains unclear. To investigate the efficacy of PIWIL1 SNPs genotype on the morbidity and mortality of GC and its interaction within PIWIL1 gene SNPs variation and between elevated plasma glucose. <b><i>Materials and Methods:</i></b> We conducted a case-control study that contained 216 GC patients and 204 cancer-free controls to compare differential expression of PIWIL1 SNPs. <b><i>Results:</i></b> PIWIL1 gene rs1106042 AA and AG genotypes were associated with significantly reduced GC risk (odds ratio [OR]: 0.15 and 0.26, <i>p</i> < 0.001 and <i>p</i> = 0.016), and rs10773771 CT+CC type significantly increased cancer risk (OR: 1.54 <i>p</i> = 0.037). We observed strong associations between rs10773771 and pathological type (<i>p</i> = 0.012), rs11703684, and invasion depth (<i>p</i> = 0.012). We noticed significant gene-gene interaction between rs1106042 and rs10773771 (<i>p</i> = 0.0107). Interaction between the copresence of rs1106042 GG plus hyperglycemia was also significant (relative excess risk due to interaction: 28.78, attributable proportion due to interaction: 68.2%, synergy index: 3.32). Patients with rs1892723 TT and rs1892722 GG+GA type had better survival (<i>p</i> = 0.030 and <i>p</i> = 0.048). <b><i>Conclusion:</i></b> rs10773771 CT+CC was associated with GC risk increase, rs1106042 AA and AG function as a protective factor. rs1892723 CT+TT and rs1892722 AA type may portend a poor prognosis. Elevated fasting plasma glucose will significantly increase the risk of PIWIL gene rs1106042 GG carcinogenesis by multiplicative interaction.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Creating a Path for Gene and Cell Therapies to Be Accessible to Patients. 为患者提供基因和细胞治疗的途径。
IF 1.4 4区 生物学 Q4 Medicine Pub Date : 2023-06-01 DOI: 10.1089/gtmb.2023.29073.hal
Helen Albert
{"title":"Creating a Path for Gene and Cell Therapies to Be Accessible to Patients.","authors":"Helen Albert","doi":"10.1089/gtmb.2023.29073.hal","DOIUrl":"https://doi.org/10.1089/gtmb.2023.29073.hal","url":null,"abstract":"","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9761766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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