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综合泛癌分析揭示 TMEM92 在肿瘤免疫微环境中的预后意义

英文原题:Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment.

查看英文原题

Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment.

PubMed 2024/04/20(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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研究概要

这些发现拓展了对 TMEM92 在肿瘤发生和进展中作用的认识,并提示 TMEM92 可能在多种恶性肿瘤中具有免疫调节作用。

研究思路结论见上方概要

跨膜蛋白92(TMEM92)已被认为可促进肿瘤进展。然而,关于TMEM92的预后意义及其在多种癌症类型中免疫反应作用方面的全面分析,仍有待阐明。

本研究的数据来源于多个公开可访问的在线平台和数据库,包括 TCGA、GTEx、UCSC Xena、CCLE、cBioPortal、HPA、TIMER2.0、GEPIA、CancerSEA、GDSC、exoRBase 和 ImmuCellAI。我们系统分析了 TMEM92 在多种癌症类型相关的人类器官、组织、细胞外囊泡(EVs)和细胞系中 mRNA 和蛋白质水平的表达模式。随后,进行了分析以确定 TMEM92 与预后、DNA 甲基化、拷贝数变异(CNV)、肿瘤微环境(TME)、免疫细胞浸润、免疫相关基因、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、错配修复(MMR)以及半数抑制浓度(IC50)值等各种参数之间的关系。

在本研究中,我们观察到TMEM92在大多数癌症类型中显著过表达,且与较差预后相关。TMEM92表达与DNA甲基化和CNV之间出现了显著关联。此外,还发现TMEM92表达、TME与免疫细胞浸润程度之间存在显著关系。有趣的是,虽然TMEM92表达与巨噬细胞存在呈正相关,但与CD8+ T细胞浸润水平呈负相关。同时,还发现TMEM92与主要组织相容性复合体、TMB、MSI和MMR之间存在显著关联。基因集富集分析和基因集变异分析的结果进一步证实了TMEM92与肿瘤发生背景中免疫和代谢通路的联系。

展开英文摘要原文

Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated.

In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values.

In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context.

These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.

论文信息

作者
Wu Z、Pan T、Li W、Zhang YH、Guo SH、Liu Y、Zhang L、Wang ZY
第一作者单位
Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Chang-an District, Shijiazhuang, 050011, Hebei, China.China
通讯作者单位
Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Chang-an District, Shijiazhuang, 050011, Hebei, China. drwangzhiyu@hebmu.edu.cn.China
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2024 Oct
原文标识
PubMed 38642258 · DOI 10.1007/s12094-024-03477-6