Table_1_Systematic Pan-Cancer Analysis Identifies TREM2 as an Immunological and Prognostic Biomarker.XLSX

Triggering receptor expressed on myeloid cells-2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although increasing evidence supports a vital role for TREM2 in tumorigenesis of some cancers, no systematic pan-cancer analysis of TREM2 is available. Thus, we aimed to explore the prognostic value, and investigate the potential immunological functions, of TREM2 across 33 cancer types. Based on datasets from The Cancer Genome Atlas, and the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and Human Protein Atlas, we employed an array of bioinformatics methods to explore the potential oncogenic roles of TREM2, including analyzing the relationship between TREM2 and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration of different tumors. The results show that TREM2 is highly expressed in most cancers, but present at low levels in lung cancer. Further, TREM2 is positively or negatively associated with prognosis in different cancers. Additionally, TREM2 expression was associated with TMB and MSI in 12 cancer types, while in 20 types of cancer, there was a correlation between TREM2 expression and DNA methylation. Six tumors, including breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, were screened out for further study, which demonstrated that TREM2 gene expression was negatively correlated with infiltration levels of most immune cells, but positively correlated with infiltration levels of M1 and M2 macrophages. Moreover, correlation with TREM2 expression differed according to T cell subtype. Our study reveals that TREM2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

髓系细胞触发受体-2（Triggering receptor expressed on myeloid cells-2, TREM2）是免疫球蛋白超家族跨膜受体，亦是介导免疫应答的多条病理通路的关键信号枢纽。尽管越来越多的证据表明TREM2在部分癌症的发生发展中发挥重要作用，但目前尚无针对TREM2的系统性泛癌分析研究。因此，本研究旨在探究TREM2在33种癌症中的预后价值，并分析其潜在的免疫学功能。本研究基于癌症基因组图谱（The Cancer Genome Atlas, TCGA）、癌症细胞系百科全书（Cancer Cell Line Encyclopedia, CCLE）、基因型组织表达数据库（Genotype Tissue-Expression, GTEx）、cBioPortal以及人类蛋白质图谱（Human Protein Atlas, HPA）的数据集，采用一系列生物信息学方法探究TREM2潜在的致癌作用，包括分析TREM2与不同肿瘤的预后、肿瘤突变负荷（tumor mutational burden, TMB）、微卫星不稳定性（microsatellite instability, MSI）、DNA甲基化以及免疫细胞浸润之间的关联。研究结果显示，TREM2在大多数癌症中呈高表达，但在肺癌中表达水平较低。此外，TREM2在不同癌症中与预后分别呈正相关或负相关。另外，TREM2表达与12种癌症的TMB和MSI存在关联，而在20种癌症中，TREM2表达与DNA甲基化水平相关。本研究筛选出6种肿瘤用于后续研究，包括乳腺浸润性癌、宫颈鳞状细胞癌及宫颈内膜腺癌、肾透明细胞癌、肺鳞状细胞癌、皮肤黑色素瘤以及胃腺癌；分析结果表明，TREM2基因表达与大多数免疫细胞的浸润水平呈负相关，但与M1、M2型巨噬细胞的浸润水平呈正相关。此外，TREM2表达与免疫细胞的相关性因T细胞亚型不同而存在差异。本研究揭示，由于TREM2在肿瘤发生发展及肿瘤免疫中的作用，其可作为多种恶性肿瘤的预后标志物。