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跨膜蛋白119(TMEM119)在胃腺癌中的作用及其对免疫的特定影响。

The role of TMEM119 in gastric adenocarcinoma and its specific effects on immunity.

作者信息

Liu Yating, Yan Xin, Qu Caihao, Tang Futian, Wang Qian, Li Yumin

机构信息

Department of Medical Oncology, Lanzhou University Second Hospital, Lanzhou, China.

Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, China.

出版信息

J Int Med Res. 2025 Apr;53(4):3000605241306668. doi: 10.1177/03000605241306668. Epub 2025 Apr 12.

Abstract

ObjectiveTo investigate the prognostic significance and immunological implication of transmembrane protein 119 (TMEM119) in stomach adenocarcinoma (STAD).MethodsThis study included STAD-associated data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, expression levels were analysed by immunohistochemistry in tissue samples from patients with STAD (with microsatellite instability or microsatellite stability). Gene Set Enrichment Analysis (GSEA) was conducted to explore signalling pathways related to TMEM119 in STAD. Additionally, CIBERSORT and ESTIMATE algorithms were applied to examine the relationship between expression and tumour-infiltrating immune cells, as well as the tumour microenvironment.ResultsSurgical specimens from 100 patients with STAD (50 each with microsatellite stability or microsatellite instability); TCGA RNA-sequence and clinical data from 375 STAD tumour tissues and 32 paracancerous tissues; and two GEO datasets (GSE27342, comprising 80 paracancerous tissues and 80 tumour tissues; and GSE84437, comprising 433 tumour samples) were analysed. TMEM119 was found to be elevated in STAD, and associated with poor prognosis. Clinical gastric cancer tissues exhibited increased expression. was enriched in immune-related functions and pathways. correlated with immune checkpoint genes, tumour mutational burden, and microsatellite instability. TMEM119 was positively correlated with tumour-infiltrating immune cells, tumour microenvironment, mannose receptor C-type I (CD206), and programmed cell death-ligand 1 (PD-L1), while inversely related to nitric oxide synthase 2.ConclusionsTMEM119 may be a potential immune-related biomarker for STAD prognosis and therapeutic targeting.

摘要

目的

探讨跨膜蛋白119(TMEM119)在胃腺癌(STAD)中的预后意义及免疫学意义。

方法

本研究纳入了从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获得的与STAD相关的数据。此外,通过免疫组织化学分析了STAD患者(微卫星不稳定或微卫星稳定)组织样本中的表达水平。进行基因集富集分析(GSEA)以探索STAD中与TMEM119相关的信号通路。此外,应用CIBERSORT和ESTIMATE算法来研究表达与肿瘤浸润免疫细胞以及肿瘤微环境之间的关系。

结果

分析了100例STAD患者的手术标本(微卫星稳定或微卫星不稳定各50例);375个STAD肿瘤组织和32个癌旁组织的TCGA RNA序列及临床数据;以及两个GEO数据集(GSE27342,包括80个癌旁组织和80个肿瘤组织;GSE84437,包括433个肿瘤样本)。发现TMEM119在STAD中升高,并与不良预后相关。临床胃癌组织中表达增加。在免疫相关功能和通路中富集。与免疫检查点基因、肿瘤突变负荷和微卫星不稳定性相关。TMEM119与肿瘤浸润免疫细胞、肿瘤微环境、甘露糖受体C型I(CD206)和程序性细胞死亡配体1(PD-L1)呈正相关,而与一氧化氮合酶2呈负相关。

结论

TMEM119可能是STAD预后和治疗靶点的潜在免疫相关生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0de3/12033527/f6f16d17bfac/10.1177_03000605241306668-fig1.jpg

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