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跨癌症的电压门控钾通道相关基因 KCNH2 的综合分析。

Integrated analysis of the voltage-gated potassium channel-associated gene KCNH2 across cancers.

机构信息

Department of Cardiovascular Medicine, First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, 515000, China.

Ningbo Institute of Innovation for Combined Medicine and Engineering, Lihuili Hospital Affiliated to Ningbo University, No. 378 Dongqing Road, Yinzhou District, Ningbo, 315000, Zhejiang, China.

出版信息

BMC Bioinformatics. 2023 Feb 15;24(1):51. doi: 10.1186/s12859-023-05180-9.

DOI:10.1186/s12859-023-05180-9
PMID:36792990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9933257/
Abstract

KCNH2 encodes the human ether-a-go-go-related gene (hERG) potassium channel and is an important repolarization reserve for regulating cardiac electrical activity. Increasing evidence suggests that it is involved in the development of various tumours, yet a thorough analysis of the underlying process has not been performed. Here, we have comprehensively examined the role of KCNH2 in multiple cancers by assessing KCNH2 gene expression, diagnostic and prognostic value, genetic alterations, immune infiltration correlations, RNA modifications, mutations, clinical correlations, interacting proteins, and associated signalling pathways. KCNH2 is differentially expressed in over 30 cancers and has a high diagnostic value for 10 tumours. Survival analysis showed that high expression of KCNH2 was associated with a poor prognosis in glioblastoma multiforme (GBM) and hepatocellular carcinoma (LIHC). Mutations and RNA methylation modifications (especially m6A) of KCNH2 are associated with its expression in multiple tumours. KCNH2 expression is correlated with tumour mutation burden, microsatellite instability, neoantigen load, and mutant-allele tumour heterogeneity. In addition, KCNH2 expression is associated with the tumour immune microenvironment and its immunosuppressive phenotype. KEGG signalling pathway enrichment analysis revealed that KCNH2 and its interacting molecules are involved in a variety of pathways related to carcinogenesis and signal regulation, such as the PI3K/Akt and focal adhesion pathways. Overall, we found that KCNH2 and its interaction molecular are expected to be immune-related biomarkers for cancer diagnosis and prognosis evaluation, and are potential regulatory targets of singalling pathways for tumour development due to their significant role in cancers.

摘要

KCNH2 编码人类 ether-a-go-go 相关基因(hERG)钾通道,是调节心脏电活动的重要复极化储备。越来越多的证据表明,它参与了各种肿瘤的发生,但尚未对其潜在机制进行全面分析。在这里,我们通过评估 KCNH2 基因表达、诊断和预后价值、遗传改变、免疫浸润相关性、RNA 修饰、突变、临床相关性、相互作用蛋白和相关信号通路,全面研究了 KCNH2 在多种癌症中的作用。KCNH2 在 30 多种癌症中表达差异,对 10 种肿瘤具有较高的诊断价值。生存分析表明,KCNH2 高表达与胶质母细胞瘤(GBM)和肝细胞癌(LIHC)的预后不良相关。KCNH2 的突变和 RNA 甲基化修饰(特别是 m6A)与其在多种肿瘤中的表达相关。KCNH2 表达与肿瘤突变负担、微卫星不稳定性、新抗原负荷和突变等位基因肿瘤异质性相关。此外,KCNH2 表达与肿瘤免疫微环境及其免疫抑制表型相关。KEGG 信号通路富集分析显示,KCNH2 及其相互作用分子参与与癌症发生和信号调节相关的多种途径,如 PI3K/Akt 和焦点黏附途径。总之,我们发现 KCNH2 及其相互作用分子有望成为癌症诊断和预后评估的免疫相关生物标志物,并且由于它们在癌症中的重要作用,可能成为肿瘤发展信号通路的潜在调节靶点。

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