TRPC6 is a Biomarker for Prognosis and Immunotherapy of Stomach Adenocarcinoma Based on Bioinformatic Analysis and Experimental Validation.

IF 6.2 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2024-12-12 eCollection Date: 2024-01-01 DOI:10.2147/ITT.S488953
Xingchi Hu, Hongwei Wang, Haitao Sun, Jingxin Zhang, ZhenXiong Ye, Zhenhua Huang
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引用次数: 0

Abstract

Background: Transient receptor potential canonical 6 (TRPC6), a key member of the TRPC family, is involved in diverse physiological and pathological processes. Although previous studies have implicated TRPC6 in the progression of stomach adenocarcinoma (STAD), its precise functions and mechanisms remain unclear. Understanding TRPC6's role in STAD may provide insights into its prognostic and therapeutic potential.

Methods: Using transcriptional and clinical data from The Cancer Genome Atlas (TCGA) database, we assessed the expression and prognostic value of TRPC6 in STAD through Kaplan-Meier survival curve analysis and correlation studies. Immune-related parameters, including immune cell infiltration and immune checkpoint gene expression, were also evaluated. Additionally, drug response analyses explored TRPC6's association with therapeutic agents. In vitro experiments were conducted to investigate TRPC6's role in STAD cell proliferation, migration, and invasion, focusing on its regulation of the PI3K-Akt signaling pathway.

Results: TRPC6 was significantly overexpressed in STAD tissues compared to normal tissues, with high TRPC6 expression associated with poor overall survival. TRPC6 expression correlated strongly with immune cell infiltration, immune checkpoint genes, and sensitivity to therapies such as Lapatinib, anti-CTLA4, and anti-PD1 treatments. Functional assays confirmed that TRPC6 promotes STAD cell proliferation, migration, and invasion by activating the PI3K-Akt signaling pathway.

Conclusion: This study highlights the prognostic significance of TRPC6 in STAD and its potential as a therapeutic target. TRPC6's involvement in immune regulation and cancer cell progression underscores its dual role in STAD pathogenesis and treatment, offering new avenues for targeted therapy development.

基于生物信息学分析和实验验证的TRPC6是胃腺癌预后和免疫治疗的生物标志物。
背景:瞬时受体电位规范6 (Transient receptor potential canonical 6, TRPC6)是TRPC家族的关键成员,参与多种生理病理过程。尽管先前的研究表明TRPC6参与胃腺癌(STAD)的进展,但其确切的功能和机制尚不清楚。了解TRPC6在STAD中的作用可能有助于了解其预后和治疗潜力。方法:利用美国癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库的转录和临床数据,通过Kaplan-Meier生存曲线分析和相关研究,评估TRPC6在STAD中的表达及其预后价值。免疫相关参数,包括免疫细胞浸润和免疫检查点基因表达,也进行了评估。此外,药物反应分析探讨了TRPC6与治疗剂的关系。我们通过体外实验研究TRPC6在STAD细胞增殖、迁移和侵袭中的作用,重点研究其对PI3K-Akt信号通路的调控。结果:与正常组织相比,TRPC6在STAD组织中显著过表达,TRPC6高表达与较差的总生存率相关。TRPC6表达与免疫细胞浸润、免疫检查点基因以及对拉帕替尼、抗ctla4和抗pd1治疗等疗法的敏感性密切相关。功能分析证实TRPC6通过激活PI3K-Akt信号通路促进STAD细胞增殖、迁移和侵袭。结论:本研究强调了TRPC6在STAD中的预后意义及其作为治疗靶点的潜力。TRPC6参与免疫调节和癌细胞进展,强调了其在STAD发病机制和治疗中的双重作用,为靶向治疗的发展提供了新的途径。
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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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