TRIM27 is an adverse prognostic biomarker and associated with immune and molecular profiles in right-sided colon cancer.

癌症研究 免疫系统 生物 癌症 结直肠癌 免疫学 遗传学
作者
Minghui Zhang,Bowen Yang,Lingyun Zhang,Xiaoyu Guo,Guangwei Zhang,Xiaofang Che,Ce Li,Kezuo Hou,Xiaojie Zhang,Jinglei Qu,Ti Wen,Xiujuan Qu
出处
期刊:PubMed [National Institutes of Health]
卷期号:12 (11): 4988-5003
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摘要

Right-sided colon cancer (RCC), as an independent tumor entity, shows a poor prognosis. It is imperative to detect immune microenvironment-related genes for predicting RCC patient prognosis and study their function in RCC. Tripartite motif-containing 27 (TRIM27) was identified as a risk signature from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets by using weighted gene co-expression network analysis, differentially expressed analysis, and univariate Cox analysis. It predicted a poorer overall survival and increased lymph node metastasis, which were then validated in our 48 clinical samples. Using immunohistochemistry, TRIM27 was found to be highly expressed in both cancer cells and surrounding immunocytes, and its expression in tumor or immune cells both predicted a poorer prognosis. Thereafter, the functional mechanism, immune and molecular characteristics of TRIM27 were investigated using gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, and gene set variation analysis (GSVA) at the single-cell, somatic mutation, and RNA-seq level. Patients with highly expressed TRIM27 presented lower CD4+ T cell infiltration and activation of the mTORC1/glycolysis pathway. In addition, patients with highly expressed TRIM27 were characterized by hypermetabolism, higher tumor purity, more BRAF mutation, and more chromosomal instability. Collectively, TRIM27 is an important immune-related prognostic biomarker in patients with RCC. It may function via activating the mTORC1/glycolysis pathway and suppressing CD4+ T cells. These results indicated that TRIM27 could be a promising therapeutic target in RCC.

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