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CYP2J2 是与肾透明细胞癌免疫浸润相关的诊断和预后生物标志物。

CYP2J2 Is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, Guangxi, China.

Center for Genomic and Personalized Medicine, Guangxi Medical University, 530021 Nanning, Guangxi, China.

出版信息

Biomed Res Int. 2021 Jun 23;2021:3771866. doi: 10.1155/2021/3771866. eCollection 2021.

DOI:10.1155/2021/3771866
PMID:34258261
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8249128/
Abstract

Cytochrome P450 family 2 subfamily J member 2 (CYP2J2), a member of the monooxygenase cytochrome P450 (CYP) family and the only member of the human CYP2J subfamily, has many functions, including regulation of oxidative stress, inflammation, apoptosis, and immune responses. However, its role in cancer development has not been clearly elucidated. In this study, expression levels of CYP2J2 in various cancer types were determined using the Oncomine, the Gene Expression Profiling Interactive Analysis (GEIPA), DriverDBv3, UALCAN, and Tumor Immune Estimation Resource (TIMER) databases. The prognostic value of CYP2J2 for KIRC was analyzed using GEPIA, UALCAN, OSkirc, and DriverDBv3 databases. We evaluated the expression levels of CYP2J2 transcript, protein, and promoter methylation at different clinical characteristics in KIRC through the UALCAN database. Simultaneously, CYP2J2 network-related functions were evaluated using the GeneMANIA interactive tool while the biological processes involved in CYP2J2 and its interactive genes were investigated through Metascape and FunRich. Then, we used TIMER to determine the correlation between CYP2J2 expression levels and immune infiltration levels in KIRC. In KIRC, the CYP2J2 gene, RNA, and protein were found to be overexpressed. However, the methylation level of CYP2J2 promoter in KIRC was lower than in normal tissues. Surprisingly, elevated expression levels of CYP2J2 exhibited better prognostic outcomes in KIRC. Evaluation of protein-protein interaction networks and biological processes revealed that CYP2J2 was principally involved in immune responses, apoptosis, and other metabolic processes. Moreover, we found that the expression levels of CYP2J2 were positively correlated with infiltration levels of B cells, CD8 + T cells, neutrophils, and dendritic cells in KIRC. Therefore, we speculated that the overexpression of CYP2J2 prolonged the survival outcome of KIRC patients, which may be related to the change of tumor immune microenvironment. Moreover, all these new understandings of CYP2J2 may provide important value for the early diagnosis and new targeted drug therapy of KIRC.

摘要

细胞色素 P450 家族 2 亚家族 J 成员 2(CYP2J2)是单加氧酶细胞色素 P450(CYP)家族的成员,也是人类 CYP2J 亚家族的唯一成员,具有许多功能,包括调节氧化应激、炎症、细胞凋亡和免疫反应。然而,其在癌症发展中的作用尚未明确阐明。在这项研究中,使用 Oncomine、基因表达谱交互式分析(GEIPA)、DriverDBv3、UALCAN 和肿瘤免疫估计资源(TIMER)数据库确定了 CYP2J2 在各种癌症类型中的表达水平。使用 GEPIA、UALCAN、OSkirc 和 DriverDBv3 数据库分析 CYP2J2 对 KIRC 的预后价值。我们通过 UALCAN 数据库评估了 CYP2J2 转录本、蛋白质和启动子甲基化在 KIRC 不同临床特征中的表达水平。同时,使用 GeneMANIA 交互式工具评估了 CYP2J2 网络相关功能,通过 Metascape 和 FunRich 研究了 CYP2J2 及其相互作用基因所涉及的生物学过程。然后,我们使用 TIMER 确定了 CYP2J2 在 KIRC 中的表达水平与免疫浸润水平之间的相关性。在 KIRC 中,CYP2J2 基因、RNA 和蛋白质均呈过表达。然而,KIRC 中 CYP2J2 启动子的甲基化水平低于正常组织。令人惊讶的是,CYP2J2 的高表达水平在 KIRC 中表现出更好的预后结果。对蛋白质-蛋白质相互作用网络和生物学过程的评估表明,CYP2J2 主要参与免疫反应、细胞凋亡和其他代谢过程。此外,我们发现 CYP2J2 的表达水平与 KIRC 中 B 细胞、CD8+T 细胞、中性粒细胞和树突状细胞的浸润水平呈正相关。因此,我们推测 CYP2J2 的过表达延长了 KIRC 患者的生存结局,这可能与肿瘤免疫微环境的变化有关。此外,对 CYP2J2 的所有这些新认识可能为 KIRC 的早期诊断和新的靶向药物治疗提供重要价值。

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