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High TCTA expression is an adverse prognostic biomarker in acute myeloid leukemia. TCTA高表达是急性髓系白血病的不良预后生物标志物。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2025-02-05 DOI: 10.1177/18758592241296287
Yunli Shao, Tong Qin

BackgroundAcute myeloid leukemia (AML) prognosis varies greatly, underscoring the need for novel biomarkers to improve patient stratification. T-cell leukemia translocation-associated gene (TCTA) has emerged as a potential player in hematological malignancies, yet its role in AML remains unexplored.ObjectiveTo investigate the prognostic significance of TCTA in AML and elucidate its functional mechanisms.MethodsRNA sequencing data from 173 AML patients (TCGA) and 70 normal controls (GTEx) were analyzed. Patients were categorized into high and low TCTA expression groups. Bioinformatics tools assessed Gene Ontology, KEGG pathways, and immune infiltration and constructed a nomogram predicting 1-5-year overall survival (OS).ResultsHigh TCTA expression correlated with significantly reduced OS (P < 0.001), with multivariate analysis identifying TCTA expression alongside age and cytogenetic risk as independent OS predictors. Receiver operating characteristic analysis validated TCTA's diagnostic potential. Enrichment analyses implicated TCTA in pathways critical to AML, such as hematopoiesis, p53 signaling, and DNA methylation, with a notable association with natural killer (NK) cell activity.ConclusionsElevated TCTA expression signifies poor prognosis in AML, positioning it as a promising prognostic biomarker. Its involvement in key AML-related pathways highlights TCTA's functional relevance and potential as a therapeutic target in AML management.

急性髓性白血病(AML)的预后差异很大,因此需要新的生物标志物来改善患者分层。t细胞白血病易位相关基因(TCTA)已成为血液系统恶性肿瘤的潜在参与者,但其在AML中的作用仍未被探索。目的探讨TCTA在急性髓性白血病中的预后意义,并阐明其作用机制。方法对173例AML患者(TCGA)和70例正常对照(GTEx)的srna测序数据进行分析。将患者分为TCTA高表达组和低表达组。生物信息学工具评估了基因本体、KEGG通路和免疫浸润,并构建了预测1-5年总生存期(OS)的nomogram。结果TCTA高表达与OS显著降低相关(P
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引用次数: 0
Predictive role of HPGD gene in carcinogenesis and immune environment monitoring in human cervical cancer. HPGD基因在人宫颈癌发生及免疫环境监测中的预测作用。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2025-03-17 DOI: 10.1177/18758592241296277
Mingzhu Zhai, Weihua Yang, Chen Zou, Shan Du, Benqing Wu, Changshan Wang, Yuanzhi Lu, Yi Zheng

Background15-Hydroxyprostaglandin dehydrogenase (15-PGDH, gene symbol HPGD) is considered a tumor suppressor, and its expression is often proportional to the anticancer response. However, the clinical significance of HPGD/15-PGDH in predicting immune response and its diagnosis and prognosis value in cervical cancer remains unclear.ObjectiveThis study aims to explore the clinical significance of HPGD/15-PGDH in predicting carcinogenesis, prognosis, and sensitivity to immuno- and chemotherapy in cervical cancer.MethodsA comprehensive evaluation of the diagnostic, treatment-sensitive, and prognostic value of HPGD/15-PGDH in cervical cancer was conducted by bioinformatics analysis of public databases and validation of real cohort data.ResultsBioinformatics analysis showed that HPGD expression was decreased in cervical cancer and did not independently predict patient prognosis. Low HPGD expression was linked to resistance to certain chemotherapies, potentially due to immunosuppression triggered by low HPGD levels. Validation in clinical samples from the local hospital confirmed the decreased 15-PGDH expression and increased COX-2 expression in HPV16-positive cervical cancer patients and increased immune suppression during cancer progression.ConclusionsHPGD/15-PGDH is a potential biomarker for predicting the progression, immune response, and chemotherapy sensitivity of cervical cancer, with implications that it is of great value for the diagnosis and individual-based treatment of cervical cancer.

15-羟基前列腺素脱氢酶(15- hydroxyprostaglandin dehydrogenase, 15-PGDH,基因符号HPGD)被认为是一种肿瘤抑制因子,其表达通常与抗癌反应成正比。然而,HPGD/15-PGDH在宫颈癌免疫应答预测中的临床意义及其诊断和预后价值尚不清楚。目的探讨HPGD/15-PGDH在宫颈癌发生、预后及免疫和化疗敏感性预测中的临床意义。方法通过对公共数据库的生物信息学分析和真实队列数据的验证,对HPGD/15-PGDH在宫颈癌中的诊断、治疗敏感性和预后价值进行综合评价。结果生物信息学分析显示,宫颈癌中HPGD表达降低,不能独立预测患者预后。低HPGD表达与对某些化疗的耐药性有关,可能是由于低HPGD水平引发的免疫抑制。当地医院临床样本的验证证实,hpv16阳性宫颈癌患者15-PGDH表达降低,COX-2表达升高,并且在癌症进展过程中免疫抑制增加。结论shpgd /15-PGDH是预测宫颈癌进展、免疫反应和化疗敏感性的潜在生物标志物,对宫颈癌的诊断和个体化治疗具有重要价值。
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引用次数: 0
A fatty acid metabolism-related genes model for predicting the prognosis and immunotherapy effect of lung adenocarcinoma. 预测肺腺癌预后及免疫治疗效果的脂肪酸代谢相关基因模型。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-12-01 Epub Date: 2025-03-17 DOI: 10.1177/18758592241296285
Lingxue Tang, Tong Wang

ObjectiveLung adenocarcinoma (LUAD) is a common and highly heterogeneous malignancy cancer with increasing morbidity and mortality. Dysregulation of fatty acid metabolism (FAM) has been identified as a key regulator of LUAD progression. Our purpose was to establish a risk model of FAM-related genes to provide a reference for the prognosis prediction of LUAD.MethodsFirstly, we screened FAM-related differentially expressed genes (DEGs) based on the Cancer Genome Atlas (TCGA) database, and identified the prognostic signatures by Cox-regression analysis. The least absolute shrinkage and selection operator algorithm (LASSO) was used to obtain the formula for risk model. And the analysis of Gene Expression Omnibus (GEO) dataset used to verify. Nomogram was produced for individualized prediction in clinical treatment. Immune cell function and drug sensitivity analysis used to screen potential therapeutic drugs.ResultsPatients in low-risk had better overall survival (OS). High-risk patients exhibit higher TMB and lower TIDE scores, and they are more likely to benefit from immunotherapy. The analysis of GEO verified that risk model has a high prediction accuracy.ConclusionThe risk model based on 17 FAM-related DEGs is of great value in predicting the prognosis of LUAD, and these prognostic signatures may be potential therapeutic targets for LUAD.

目的肺腺癌(LUAD)是一种常见病和高度异质性的恶性肿瘤,发病率和死亡率均呈上升趋势。脂肪酸代谢失调(FAM)已被确定为LUAD进展的关键调节因子。我们的目的是建立fam相关基因的风险模型,为LUAD的预后预测提供参考。方法首先基于癌症基因组图谱(Cancer Genome Atlas, TCGA)数据库筛选fam相关差异表达基因(differential expression genes, deg),并通过Cox-regression分析识别预后特征。采用最小绝对收缩和选择算子算法(LASSO)得到风险模型的计算公式。并利用GEO数据集进行分析验证。生成Nomogram用于临床治疗的个体化预测。免疫细胞功能和药物敏感性分析用于筛选潜在的治疗药物。结果低危组患者总生存期(OS)较低。高危患者表现出较高的TMB和较低的TIDE评分,他们更有可能从免疫治疗中获益。GEO分析验证了风险模型具有较高的预测精度。结论基于17个fam相关deg的风险模型对LUAD的预后预测具有重要价值,这些预后特征可能是LUAD潜在的治疗靶点。
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引用次数: 0
Mechanism study of serum extracellular nano-vesicles miR-412-3p targeting regulation of TEAD1 in promoting malignant biological behavior of sub-centimeter lung nodules. 血清细胞外纳米载体 miR-412-3p 靶向调控 TEAD1 促进厘米以下肺结节恶性生物学行为的机制研究
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-23 DOI: 10.3233/cbm-240137
Yuxia Deng,Nishant Patel,Shuang Ding,Haijun Zhang
OBJECTIVETo investigate the impact and potential mechanisms of serum extracellular nano-vesicles (sEVs) miR-412-3p released from sub-centimeter lung nodules with a diameter of ⩽ 10 mm on the malignant biological function of micro-nodular lung cancer (mnLC).METHODSA total of 87 participants were included and divided into a mnLC group (n= 30), a benign lung nodule (BLN) group (n= 27), and a healthy people control group (n= 30). Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot (WB) were used to measure the morphological characteristics and surface markers of sEVs. In vitro analysis, real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8 cell proliferation assay, clone formation assay, Transwell, stem cell sphere-forming assay, and WB assay were conducted to verify the effect of miR-412-3p/TEAD1 signaling axis on the biological function of lung cancer cells through, respectively. Further validation was conducted using the serum sEVs of the participants.RESULTSThe expression level of sEVs-miR-412-3p in the mnLC group was significantly higher than that in the BLN and healthy groups (P< 0.01). In lung cancer cell lines, miR-412-3p can negatively regulate the targeted gene TEAD1. The miR-412-3p/TEAD1 signaling axis is involved in promoting the EMT signaling pathway and regulating the malignant biological functions of lung cancer cell proliferation, migration, and stemness (P< 0.05). In addition, sEVs in the mnLC group significantly promoted lung cancer cell proliferation, migration, and stemness compared to the BLN and healthy groups, inhibited the expression of E-cadherin and TEAD1 in lung cancer cells, and promoted the expression of N-cadherin and Vimentin (P< 0.05).CONCLUSIONsEVs-miR-412-3p could promote the biological process of EMT, and lead to the occurrence of malignant biological behavior in sub-centimeter lung nodules. This provides evidence for the miR-412-3p/TEAD1 signaling axis as a potential therapeutic target for mnLC.
目的研究直径⩽ 10 mm的亚厘米肺结节释放的血清细胞外纳米载体(sEVs)miR-412-3p对微结节性肺癌(mnLC)恶性生物学功能的影响和潜在机制。方法共纳入 87 名参与者,分为微小结节肺癌组(30 人)、良性肺结节组(27 人)和健康人对照组(30 人)。透射电子显微镜(TEM)、纳米颗粒追踪分析(NTA)和 Western 印迹(WB)用于测量 sEVs 的形态特征和表面标记物。在体外分析中,通过实时定量聚合酶链反应(RT-qPCR)、CCK-8细胞增殖试验、克隆形成试验、Transwell、干细胞球形成试验和WB试验分别验证了miR-412-3p/TEAD1信号轴对肺癌细胞生物学功能的影响。结果mnLC组sEVs-miR-412-3p的表达水平明显高于BLN组和健康组(P< 0.01)。在肺癌细胞系中,miR-412-3p 能负向调节靶基因 TEAD1。miR-412-3p/TEAD1信号轴参与促进EMT信号通路,调控肺癌细胞增殖、迁移和干性等恶性生物学功能(P< 0.05)。此外,与 BLN 组和健康组相比,mnLC 组中的 sEVs 能显著促进肺癌细胞的增殖、迁移和干性,抑制肺癌细胞中 E-cadherin 和 TEAD1 的表达,促进 N-cadherin 和 Vimentin 的表达(P< 0.05)。这为 miR-412-3p/TEAD1 信号轴作为 mnLC 的潜在治疗靶点提供了证据。
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引用次数: 0
Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab. 循环肿瘤 DNA (ctDNA) 作为 Nivolumab 治疗晚期肝细胞癌疗效的生物标记物。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-21 DOI: 10.3233/cbm-230431
Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb
BACKGROUNDCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).OBJECTIVEThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.METHODSWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.RESULTSOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).CONCLUSIONSctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.
背景循环肿瘤DNA(ctDNA)是肝细胞癌(HCC)检测、诊断、治疗选择和预后判断的一种很有前景的非侵入性标记物。目的本研究旨在检验ctDNA作为预后和预测工具在接受尼伐单抗治疗的HCC患者中的实用性。方法我们利用市售平台上的综合基因组检测分析了44名HCC患者治疗前的ctDNA。我们利用对数秩检验和单变量 Cox 模型将总生存期(OS)和无进展生存期(PFS)与 ctDNA 表达相关联。除3名患者外,所有患者都至少发现了一种基因改变,TP53是最常见的改变基因(52.3%)。中位OS为17.5个月(95% CI:12.7,NA)。涉及PIK3CA、BRCA1和CCND1扩增的基因突变与较短的OS相关(P分别为0.0001、0.0001和0.01)。中位生存时间为4.01个月(95% CI:3.06,9.33)。涉及KIT和PIK3CA的突变与较短的PFS相关(P分别为0.0001和0.0004),而涉及CTNNB1的突变与较长的PFS相关(P= 0.04)。需要未来的研究加以证实。
{"title":"Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.","authors":"Yehia I Mohamed,Sunyoung S Lee,Tarik Demir,Shadi Chamseddine,Zishuo Ian Hu,Lianchun Xiao,Khaled Elsayes,Jeffrey S Morris,Robert A Wolff,Rikita Hiatia,Aliya Qayyum,Asif Rashid,Dan G Duda,James C Yao,Michael LaPelusa,Eugene J Koay,Armeen Mahvash,Ahmed Al Azzam,Ecaterina E Dumbrava,Manal Hassan,Hesham M Amin,Ahmed Omar Kaseb","doi":"10.3233/cbm-230431","DOIUrl":"https://doi.org/10.3233/cbm-230431","url":null,"abstract":"BACKGROUNDCirculating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).OBJECTIVEThis study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.METHODSWe analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.RESULTSOf 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04).CONCLUSIONSctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"23 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258328","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
Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients. 机器学习确定了用于早期检测慢性萎缩性胃炎患者的 5 种血清细胞因子面板。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-05 DOI: 10.3233/cbm-240023
Fangmei An,Yan Ge,Wei Ye,Lin Ji,Ke Chen,Yunfei Wang,Xiaoxue Zhang,Shengrong Dong,Yao Shen,Jiamin Zhao,Xiaojuan Gao,Simon Junankar,Robin Barry Chan,Dimitris Christodoulou,Wen Wen,Peihua Lu,Qiang Zhan
BACKGROUNDChronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized.METHODSBlood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm.RESULTSFive serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59).CONCLUSIONUsing state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions.FUNDINGSupported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).
背景:慢性萎缩性胃炎(CAG)是胃癌(GC)的高危癌前病变。早期准确检测 CAG 并将其与良性胃炎(如慢性浅表性胃炎,CSG)区分开来对于胃癌的最佳治疗至关重要。然而,目前尚缺乏诊断 CAG 的准确非侵入性方法。方法收集 247 名接受内镜筛查的患者的血样,并使用多重免疫测定法量化 40 种细胞因子。患者被分为发现组和验证组。使用特征选择算法 Boruta 对每种细胞因子的重要性进行排序。结果确定了能区分 CAG 和 CSG 患者的五种血清细胞因子(IL-10、TNF-α、Eotaxin、IP-10 和 SDF-1a),并将其用于构建预测模型。该模型非常稳健,能高效识别 CAG 患者(AUC = 0.88,准确率 = 0.78)。结论利用最先进的 ML 和血液免疫测定技术,我们开发出了一种用于检测 GC 癌前病变的改进型无创筛查方法。BK20211039);无锡市卫生委员会中青年拔尖人才支持计划(BJ2023008);无锡市卫生委员会医学重点学科计划(ZDXK2021010),无锡市科技局项目(编号:N20201004);无锡市卫生委员会科研计划(Z202208,J202104)。
{"title":"Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients.","authors":"Fangmei An,Yan Ge,Wei Ye,Lin Ji,Ke Chen,Yunfei Wang,Xiaoxue Zhang,Shengrong Dong,Yao Shen,Jiamin Zhao,Xiaojuan Gao,Simon Junankar,Robin Barry Chan,Dimitris Christodoulou,Wen Wen,Peihua Lu,Qiang Zhan","doi":"10.3233/cbm-240023","DOIUrl":"https://doi.org/10.3233/cbm-240023","url":null,"abstract":"BACKGROUNDChronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized.METHODSBlood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm.RESULTSFive serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59).CONCLUSIONUsing state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions.FUNDINGSupported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258330","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
Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma. p元素诱导的睾丸萎缩(PIWI)转录物的表达模式升高是肝细胞癌的潜在候选标志物。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.3233/CBM-230134
Gehan Hammad, Samah Mamdouh, Dina Mohamed Seoudi, Mohamed Ismail Seleem, Gehan Safwat, Rania Hassan Mohamed

Background: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features.

Methods: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis.

Results: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant.

Conclusion: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.

背景:P-Element-induced wimpy testis (PIWI)蛋白与PIWI相互作用RNA (piRNA)结合,参与生殖细胞基因表达的表观遗传调控。已经发现不同类型的肿瘤细胞表现出piRNA、piwill - mrna和蛋白质的异常表达。我们旨在确定PIWIL1、PIWIL2、PIWIL3和PIWIL4在肝细胞癌患者中的mRNA表达谱,并将其表达模式与临床病理特征联系起来。方法:采用实时定量聚合酶链反应(RT-QPCR)技术检测肝癌患者组织和血清中PIWIL1、PIWIL2、PIWIL3、PIWIL4 mRNA的表达模式,通过ROC曲线评估其对诊断的影响,确定预后效用,并进行预测变异检测、与HCC microrna的相关性和网络分析。结果:HCC组织和血清样本中的表达水平均显著高于各自的对照组(p< 0.001)。此外,对诊断性能进行评估,发现风险测定具有统计学意义。结论:PIWIL mrna在HCC组织和血清样本中过表达,其表达模式与年龄、肿瘤分级和类型相关,可能是HCC有价值的分子标志物。据我们所知,我们的研究首次报道了所有PIWIL mRNA的表达水平,并表明它们作为诊断和预后生物标志物的显著价值,以及它们与HCC发展的相关性。此外,通过DDX4和miR-124-3p对HCC和PIWIL基因进行miRNA预测也可能是一种治疗机会。
{"title":"Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma.","authors":"Gehan Hammad, Samah Mamdouh, Dina Mohamed Seoudi, Mohamed Ismail Seleem, Gehan Safwat, Rania Hassan Mohamed","doi":"10.3233/CBM-230134","DOIUrl":"10.3233/CBM-230134","url":null,"abstract":"<p><strong>Background: </strong>P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features.</p><p><strong>Methods: </strong>The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis.</p><p><strong>Results: </strong>Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant.</p><p><strong>Conclusion: </strong>PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"95-111"},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11002723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479472","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
Uncovering the link between human endogenous retroviruses, inflammatory pathways, and gastric cancer development. 揭示人类内源性逆转录病毒、炎症途径和胃癌发展之间的联系。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.3233/CBM-230417
Zhengtai Li, Hongjiang Li, Kun Fang, Xinglei Lin, Changyuan Yu

Background: Endogenous retroviruses, previously deemed "junk" DNA, have gained attention in recent scientific studies. These inherited genomic elements are now recognized for their potential roles in diseases, especially cancer, highlighting their value as potential diagnostic or therapeutic targets.

Objective: This research aims to explore the association between human endogenous retroviruses (HERV) and gastric cancer, focusing on discerning HERV expression patterns and understanding their implications in gastric cancer pathology.

Methods: A quantitative analysis of HERV expression was conducted, employing Support Vector Machine (SVM) and AdaBoost algorithms to identify discriminative HERVs. The co-regulation network between protein-coding genes and HERVs was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA).

Results: Three distinct HERVs (LTR16A|72|451, LTR91|636|874, LTR27D|87|222) were identified as significantly different. Strong correlations were found between HERVs, and gene sets enriched in the inflammatory pathway.

Conclusions: HERVs appear to influence abnormal inflammatory responses, suggesting a pivotal role in gastric cancer development.

背景:内源性逆转录病毒以前被认为是 "垃圾 "DNA,但在最近的科学研究中却受到了关注。这些遗传的基因组元素因其在疾病(尤其是癌症)中的潜在作用而得到认可,凸显了其作为潜在诊断或治疗靶点的价值:本研究旨在探讨人类内源性逆转录病毒(HERV)与胃癌之间的关联,重点是识别 HERV 的表达模式并了解其在胃癌病理学中的意义:方法:采用支持向量机(SVM)和 AdaBoost 算法对 HERV 表达进行定量分析,以识别具有鉴别力的 HERV。利用加权基因共表达网络分析(WGCNA)构建了蛋白编码基因与 HERV 之间的共调控网络:结果:发现三个不同的 HERVs(LTR16A|72|451、LTR91|636|874、LTR27D|87|222)存在显著差异。HERVs与富集在炎症通路中的基因集之间存在很强的相关性:结论:HERVs 似乎会影响异常炎症反应,这表明其在胃癌的发展中起着关键作用。
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引用次数: 0
Long non-coding RNAs PTENP1, GNG12-AS1, MAGI2-AS3 and MEG3 as tumor suppressors in breast cancer and their associations with clinicopathological parameters. 作为乳腺癌肿瘤抑制因子的长非编码 RNA PTENP1、GNG12-AS1、MAGI2-AS3 和 MEG3 及其与临床病理参数的关系。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.3233/CBM-230259
Luděk Záveský, Eva Jandáková, Vít Weinberger, Luboš Minář, Milada Kohoutová, Ondřej Slanař

Background: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease.

Objective: Evaluation of novel long non-coding RNAs biomarkers for breast cancer.

Methods: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics.

Results: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality.

Conclusions: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.

背景:乳腺癌是全球最常见的癌症,也是女性死于癌症的主要原因。新型生物标志物是治疗这种疾病的重要手段:评估乳腺癌的新型长非编码 RNA 生物标志物:研究包括通过筛选分析 71 个候选 lncRNA 的表达,其中 6 个(4 个表达不足,2 个表达过高)通过 qPCR 验证和分析了 NST 乳腺癌相关肿瘤组织中的表达,并与良性样本及其临床病理特征进行了比较:结果表明:PTENP1、GNG12-AS1、MEG3 和 MAGI2-AS3 具有肿瘤抑制作用。PTENP1和GNG12-AS1的低水平表达与无进展生存率和总生存率的恶化有关。GNG12-AS1表达的降低与晚期分期有关。分期越高,PTENP1、GNG12-AS1 和 MAGI2-AS3 的表达越低。MEG3和PTENP1水平的降低与Ki-67阳性有关。NRSN2-AS1和UCA1 lncRNA过表达;UCA1水平较高与多灶性有关:结果表明,所研究的lncRNAs可能在乳腺癌中发挥重要作用,是临床研究中应进一步评估的潜在因素。
{"title":"Long non-coding RNAs PTENP1, GNG12-AS1, MAGI2-AS3 and MEG3 as tumor suppressors in breast cancer and their associations with clinicopathological parameters.","authors":"Luděk Záveský, Eva Jandáková, Vít Weinberger, Luboš Minář, Milada Kohoutová, Ondřej Slanař","doi":"10.3233/CBM-230259","DOIUrl":"10.3233/CBM-230259","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease.</p><p><strong>Objective: </strong>Evaluation of novel long non-coding RNAs biomarkers for breast cancer.</p><p><strong>Methods: </strong>The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics.</p><p><strong>Results: </strong>The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality.</p><p><strong>Conclusions: </strong>The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.</p>","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":" ","pages":"61-78"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567654","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
A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer. 基于 lncRNA-miRNA-mRNA 基因特征的风险模型,用于预测膀胱癌患者的预后。
IF 3.1 4区 医学 Q3 ONCOLOGY Pub Date : 2024-01-01 DOI: 10.3233/CBM-230216
Zhi Yi Zhao, Yin Cao, Hong Liang Wang, Ling Yun Liu

Objectives: We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC.

Methods: We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507.

Results: Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1-penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group's OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score.

Conclusions: The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.

研究目的我们旨在分析膀胱癌(BC)患者的lncRNAs、miRNAs和mRNA表达谱,从而建立一个基于基因特征的风险模型来预测BC患者的预后:我们从癌症基因组图谱(TCGA)中下载了lncRNA、miRNA和mRNA的表达数据作为训练队列,其中包括19个健康对照样本和401个BC样本。利用limma软件包筛选差异表达的RNA(DER),并利用cytoscape构建和可视化竞争性内源性RNA(ceRNA)调控网络。通过筛选候选 DERs,构建了预测 BC 患者总生存(OS)时间和预后的风险评分模型和提名图。结果显示,13个候选的lncRNA在预测BC患者总生存期(OS)和预后方面具有重要价值:结果:根据利用 L1 惩罚算法筛选出的 13 个 lncRNA、miRNA 和 mRNA,BC 患者被分为两组:高危组(包括 201 名患者)和低危组(包括 200 名患者)。在训练队列中,高风险组的OS时间(危险比[HR],2.160;95% CI,1.586~2.942;P= 5.678e-07)比低风险组的OS时间(HR,1.675;95% CI,1.037~2.713;P= 3.393e-02)要差。训练数据集和验证数据集的曲线下面积(AUC)均为 0.852。年轻患者(年龄⩽ 60 岁)的 OS 比高龄患者(年龄大于 60 岁)有所改善(HR 1.033,95% CI 1.017 至 1.049;P= 2.544E-05)。我们通过使用提名图,包括年龄、复发率和预后评分等临床病理因素,建立了基于TCGA队列的预测模型:基于13种DERs模式的风险模型可以很好地预测BC患者的预后。
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Cancer Biomarkers
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