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人类肿瘤中ADGRE5基因的综合分析:临床相关性、预后意义及个性化免疫治疗潜力

Comprehensive analysis of ADGRE5 gene in human tumors: Clinical relevance, prognostic implications, and potential for personalized immunotherapy.

作者信息

Zhang Xiangjian, Zhang Xinxin, Yang Qiuhui, Han Ruokuo, Fadhul Walaa, Sachdeva Alisha, Zhang Xianbo

机构信息

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Department of Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.

出版信息

Heliyon. 2024 Mar 7;10(6):e27459. doi: 10.1016/j.heliyon.2024.e27459. eCollection 2024 Mar 30.

DOI:10.1016/j.heliyon.2024.e27459
PMID:38501000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10945187/
Abstract

PURPOSE

The Adhesion G protein receptor E5 (ADGRE5) gene is involved in a wide range of biological functions in human tumors; however, its specific molecular mechanism and significance in the analysis of human tumors have not yet been determined. Here, we provide a comprehensive genomic architecture of ADGRE5 in the tumor immune microenvironment and its clinical relevance across a broad range of solid tumors.

METHODS

In this study, we used publicly available bioinformatics databases, with a primary focus on The Cancer Genome Atlas (TCGA) database and GTEx data, to conduct a comprehensive analysis of the impact on patient prognosis associated with ADGRE5.

RESULTS

Statistics of more than 30 solid tumors from TCGA and Cancer Cell Line Encyclopedia (CCLE) were examined. ADGRE5 was differentially expressed in several cancers and was significantly associated with survival outcomes. Higher ADGRE5 levels were associated with worse prognosis in adrenocortical carcinoma, low grade glioma of the brain (LGG), lung squamous cell carcinoma, liver hepatocellular carcinoma, and uveal melanoma (UVM). Additionally, ADGRE5 was found to be an independent risk factor for LGG and UVM. The clinical relevance of ADGRE5 in tumor immunogenicity was further investigated. The expression level of ADGRE5 was not only strongly associated with tumor infiltration, such as tumor-infiltrating immune cells and immune subtypes, but also with tumor mutation burden, pyroptosis, and epithelial-mesenchymal transition in various types of cancer (P < 0.05). Furthermore, we noted that ADGRE5 exhibited a positive association with targeted drug sensitivity and conversely, a negative association with traditional chemotherapeutic drug sensitivity. Thus, ADGRE5 is expected to be a guiding marker gene for clinical prognosis and personalized tumor immunotherapy.

摘要

目的

黏附G蛋白偶联受体E5(ADGRE5)基因参与人类肿瘤的多种生物学功能;然而,其在人类肿瘤分析中的具体分子机制和意义尚未确定。在此,我们提供了ADGRE5在肿瘤免疫微环境中的全面基因组结构及其在多种实体瘤中的临床相关性。

方法

在本研究中,我们使用公开可用的生物信息学数据库,主要关注癌症基因组图谱(TCGA)数据库和GTEx数据,对与ADGRE5相关的患者预后影响进行综合分析。

结果

对来自TCGA和癌细胞系百科全书(CCLE)的30多种实体瘤进行了统计分析。ADGRE5在几种癌症中差异表达,并与生存结果显著相关。ADGRE5水平较高与肾上腺皮质癌、脑低级别胶质瘤(LGG)、肺鳞状细胞癌、肝细胞肝癌和葡萄膜黑色素瘤(UVM)的预后较差相关。此外,ADGRE5被发现是LGG和UVM的独立危险因素。进一步研究了ADGRE5在肿瘤免疫原性中的临床相关性。ADGRE5的表达水平不仅与肿瘤浸润密切相关,如肿瘤浸润免疫细胞和免疫亚型,还与各种癌症中的肿瘤突变负担、细胞焦亡和上皮-间质转化相关(P < 0.05)。此外,我们注意到ADGRE5与靶向药物敏感性呈正相关,相反,与传统化疗药物敏感性呈负相关。因此,ADGRE5有望成为临床预后和个性化肿瘤免疫治疗的指导标志物基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/4333a0714055/gr10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/9ea0faf4ffdb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/86ad01e34ba4/gr6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/4333a0714055/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/4d75ba2612dc/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/a535edd51bf3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/fd3f5a28f280/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/c3ebf852c4b4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/9ea0faf4ffdb/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/86ad01e34ba4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/643a05134ded/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/da51e707f3b1/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/963e788e4b08/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6389/10945187/4333a0714055/gr10.jpg

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