TXNIP基因在胃腺癌组织中的表达及其与患者总生存期的关系

Zahra Shahsavar Haghighi, A. Farhadi, Sara Rafi Taheri, E. Hazrati, R. Heidari, Mohammad Foad Heidari, M. Rajaeinejad, Fatemeh Khodabandehloo, Javad Behroozi
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摘要

背景。胃癌是一种常见的胃肠道肿瘤,其发病率呈上升趋势。胃癌的发病机制非常复杂,目前仍不清楚。近年来胃癌的基础研究主要集中在基因表达异常上。越来越多的证据表明,硫氧还蛋白相互作用蛋白(TXNIP)在多种恶性肿瘤中异常表达,但在胃癌中却不清楚。本研究旨在比较TXNIP基因在胃癌癌组织及癌旁组织中的表达情况,评价其在胃癌患者预后及生存分析中的临床意义。方法。GC患者的肿瘤组织和边缘非肿瘤对照组织共50例。实时荧光定量PCR检测TXNIP基因表达水平。同时,采用生物信息学方法评估两组不同GC患者中TXNIP的表达。还进行了一项数据挖掘研究,以确定TXNIP表达在GC总生存期中的预后作用。此外,利用TCGA数据对TXNIP的泛癌表达进行分析。结果。TXNIP基因在肿瘤样品中下调,变化倍数为0.33倍,生物信息学分析重复相同的结果。TXNIP表达降低与转移、分化不良和药物滥用有显著相关性。我们的结果证明TXNIP基因表达水平与胃癌患者的总生存率呈正相关。TCGA数据的泛癌分析显示TXNIP在多种恶性肿瘤中下调。结论。本研究确立了TXNIP低表达作为胃癌预后的生物标志物。它还揭示了TXNIP表达的降低可能有利于转移性胃癌。实际意义。评估TXNIP的表达对胃癌患者的预后有重要意义。
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Evaluation of the TXNIP gene expression in gastric adenocarcinoma and its relationship with overall survival of patients
Background. Gastric Cancer (GC) is a common gastrointestinal tumor, and its incidence is increasing. The pathogenesis of GC is very complex and remains unclear. Recent basic studies of GC have focused on gene expression dysregulation. Accumulating evidence has demonstrated that thioredoxin-interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors but it is obscure in GC. This study aimed to compare the expression of the TXNIP gene in cancerous and adjacent tissue of gastric cancer and evaluate its clinical significance in the prognosis and survival analysis of gastric cancer patients. Methods. A total of 50 tumor tissues and marginal non-tumor control tissues were obtained from GC patients. Also, TXNIP gene expression levels were evaluated by real-time PCR. Meanwhile, bioinformatic approaches were used to evaluate TXNIP expression in two different cohorts of GC patients. A data mining study was also performed to determine the prognostic role of TXNIP expression in the overall survival of GC. Furthermore, a pan-cancer analysis of TXNIP expression was performed using TCGA data. Results. The TXNIP gene was down-regulated in tumor samples with a fold change of 0.33, and the same results were repeated in bioinformatics analysis. Decreased expression of TXNIP was significantly associated with metastasis, poor differentiation, and drug abuse. Our results provided evidence that TXNIP gene expression level is positively correlated with the overall survival of GC patients. Pan-cancer analysis of TCGA data revealed down-regulated TXNIP in a variety of malignant tumors. Conclusion. This study established low TXNIP expression as a prognostic biomarker in GC. It also revealed that the decrease in TXNIP expression likely favors metastatic GC. Practical Implications. Evaluation of TXNIP expression is informative in the prognosis of GC patients.
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