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含三联基序蛋白16表达在胃癌患者中的预后意义

Prognostic Significance of Tripartite Motif Containing 16 Expression in Patients with Gastric Cancer.

作者信息

Afshar Jalil, Mehrzad Jamshid, Mehrad-Majd Hassan, Goshayeshi Ladan, Saeidi Jafar

机构信息

Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Asian Pac J Cancer Prev. 2021 Aug 1;22(8):2445-2451. doi: 10.31557/APJCP.2021.22.8.2445.

Abstract

BACKGROUND AND AIM

Tripartite Motif Containing 16 (TRIM16) is a member of the TRIM protein family which is known to play a suppressor role in development of numerous tumor types. However, a positive correlation between TRIM16 expression and gastric cancer (GC) progress has created a controversial situation that need to be fully delineated.  The aim of this study was to assess the expression level of TRIM16 mRNA and its relationship with β-catenin, CyclinD, and BCL2 expression in Iranian GC patients and to investigate its possible association with patients' overall survival.  Materials and Methods: The expression level of TRIM16 of fresh primary tumor and adjacent normal tissues in 40 GC patients was evaluated by real-time quantitative PCR method. Moreover, patients were subdivided into high or low expression subgroups based on the TRIM16 expression levels. The relationship between TRIM16 expression level, β-catenin, Cyclin D, BCL2, some clinicopathological data and prognosis of GC patients was also analyzed.

RESULTS

qPCR analysis showed a lower level of TRIM16 in GC tissues (fold change=0.351) in comparison to their matched adjacent noncancerous tissues (p <0.001). Contrary to this, the expression levels of β-catenin, Cyclin D, and BCL2 genes were up-regulated in cancerous samples. This may explain the tumor suppressive function of TRIM16 in GC; as reduction in TRIM16 expression leads to the accumulation of mRNAs from β-catenin, Cyclin D, and BCL2 genes and eventually cancer progression. We did not observe any significant correlation between TRIM16 expression and patients' overall survival. Univariate Cox regression analysis indicated that anemia, weight loss, bleeding, stomach ache, and smoking are statistically associated with overall survival; while, multivariate analysis did not support any correlation.  Conclusions: In sum, this study suggests a tumor suppressive role for TRIM16 in gastric cancer and proposes it as a potential candidate for GC prognosis.
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摘要

背景与目的

含三联基序蛋白16(TRIM16)是TRIM蛋白家族的成员,已知其在多种肿瘤类型的发生发展中发挥抑制作用。然而,TRIM16表达与胃癌(GC)进展之间的正相关关系引发了一种有争议的情况,需要全面阐明。本研究的目的是评估伊朗GC患者中TRIM16 mRNA的表达水平及其与β-连环蛋白、细胞周期蛋白D和BCL2表达的关系,并探讨其与患者总生存期的可能关联。材料与方法:采用实时定量PCR法评估40例GC患者新鲜原发性肿瘤及癌旁正常组织中TRIM16的表达水平。此外,根据TRIM16表达水平将患者分为高表达或低表达亚组。还分析了TRIM16表达水平、β-连环蛋白、细胞周期蛋白D、BCL2、一些临床病理数据与GC患者预后之间的关系。

结果

qPCR分析显示,与配对的癌旁非癌组织相比,GC组织中TRIM16水平较低(倍数变化=0.351)(p<0.001)。与此相反,癌组织样本中β-连环蛋白、细胞周期蛋白D和BCL2基因的表达水平上调。这可能解释了TRIM16在GC中的肿瘤抑制功能;因为TRIM16表达降低会导致β-连环蛋白、细胞周期蛋白D和BCL2基因的mRNA积累,最终导致癌症进展。我们未观察到TRIM16表达与患者总生存期之间存在任何显著相关性。单因素Cox回归分析表明,贫血、体重减轻、出血、胃痛和吸烟与总生存期在统计学上相关;而多因素分析不支持任何相关性。结论:总之,本研究表明TRIM16在胃癌中具有肿瘤抑制作用,并提出其作为GC预后的潜在候选指标。

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