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综合泛癌分析证实FCGR3A是一种与肿瘤免疫相关的候选生物标志物。

Integrative Pan-Cancer Analysis Confirmed that FCGR3A is a Candidate Biomarker Associated With Tumor Immunity.

作者信息

Li Lilin, Huang Zijian, Du Kunpeng, Liu Xiang, Li Chunhui, Wang Duanyu, Zhang Yangfeng, Wang Changqian, Li Jiqiang

机构信息

Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, China.

Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Front Pharmacol. 2022 May 20;13:900699. doi: 10.3389/fphar.2022.900699. eCollection 2022.

Abstract

Fc gamma receptor 3A (FCGR3A) encodes a receptor for the Fc portion of immunoglobulin G, which plays a significant role in the immune response. However, the role of FCGR3A in cancers remains unclear. This study aimed to visualize the prognostic landscape of FCGR3A in pan-cancer and investigate the relationship between FCGR3A expression and tumor microenvironment. Based on the TCGA database, GTEx database, and GDSC database, we analyzed the expression of FCGR3A in pan-cancers and adjacent normal tissues and its relationship with prognosis, immune cells infiltration, immune-related genes, DNA mismatch repair (MMR) genes, DNA methylation, and drugs sensitivity. The gene alteration frequency of FCGR3A was acquired on the cBioportal website. Moreover, we constructed PPI networks, performed GO and KEGG analysis to illustrate the function, and signaling pathways of FCGR3A-related genes, and conducted gene set enrichment analysis (GSEA) of FCGR3A to further explore its potential biological functions. The differential analysis results of the publicly available databases showed that FCGR3A was generally highly expressed in pan-cancer. Survival analysis revealed that FCGR3A predominated as a risk prognostic factor in most cancers. Additionally, the expression of FCGR3A was confirmed to be associated with several immune cells infiltration, multiple immune checkpoint genes, and DNA mismatch repair genes expression in generalized carcinoma. We also identified a negative correlation between FCGR3A and DNA methylation levels. Through GO/KEGG and GESA, we found that FCGR3A was involved in many pathologic and physiological processes, and was most closely related to tumor immune-related pathways. Drug sensitivity analysis showed that higher FCGR3A expression predicts a low IC50 value for the vast majority of drugs. FCGR3A may be an immune-oncogenic molecule that correlates with tumor immune infiltration levels and affects drug sensitivity, thus it can be served as a promising biomarker for cancer detection, prognosis, therapeutic design, and follow-up.

摘要

Fcγ受体3A(FCGR3A)编码免疫球蛋白G的Fc部分的受体,其在免疫反应中起重要作用。然而,FCGR3A在癌症中的作用仍不清楚。本研究旨在可视化泛癌中FCGR3A的预后情况,并研究FCGR3A表达与肿瘤微环境之间的关系。基于TCGA数据库、GTEx数据库和GDSC数据库,我们分析了FCGR3A在泛癌和癌旁正常组织中的表达及其与预后、免疫细胞浸润、免疫相关基因、DNA错配修复(MMR)基因、DNA甲基化和药物敏感性的关系。FCGR3A的基因改变频率在cBioportal网站上获取。此外,我们构建了蛋白质-蛋白质相互作用(PPI)网络,进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析以阐明FCGR3A相关基因的功能和信号通路,并对FCGR3A进行基因集富集分析(GSEA)以进一步探索其潜在生物学功能。公开可用数据库的差异分析结果表明,FCGR3A在泛癌中通常高表达。生存分析显示,FCGR3A在大多数癌症中是主要的风险预后因素。此外,在广义癌中,FCGR3A的表达被证实与多种免疫细胞浸润、多个免疫检查点基因和DNA错配修复基因表达相关。我们还发现FCGR3A与DNA甲基化水平呈负相关。通过GO/KEGG和GESA分析发现,FCGR3A参与许多病理和生理过程,且与肿瘤免疫相关通路关系最为密切。药物敏感性分析表明,FCGR3A表达越高,绝大多数药物的半数抑制浓度(IC50)值越低。FCGR3A可能是一种免疫致癌分子,与肿瘤免疫浸润水平相关并影响药物敏感性,因此它可作为癌症检测、预后、治疗设计及随访的有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a89b/9163829/54fe97bf5f3e/fphar-13-900699-g001.jpg

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