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全面分析 KCNJ14 钾离子通道作为癌症进展和发展的生物标志物。

Comprehensive Analysis of KCNJ14 Potassium Channel as a Biomarker for Cancer Progression and Development.

机构信息

Department of Biochemistry, College of Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia.

出版信息

Int J Mol Sci. 2023 Jan 20;24(3):2049. doi: 10.3390/ijms24032049.

Abstract

Cancer is a global epidemic that has affected millions of lives. Discovering novel cancer targets is widely viewed as a key step in developing more effective therapies for cancer and other fatal illnesses. More recently, potassium (K) channels have been studied as a potential biological target for the creation of cancer treatments. Potassium Inwardly Rectifying Channel Subfamily J Member 14 (KCNJ14) is one of the cancer genome's least investigated genes. This study conducted a comprehensive examination of the relationships between KCNJ14 gene expression analysis, survival, RNA modification, immunotherapy participation, and cancer stemness using several databases. KCNJ14 was shown to be dysregulated in a variety of cancers, including lung, intestinal, head and neck, oesophageal, and stomach. Additionally, KCNJ14 was shown to be linked to RNA and DNA stemness in 18 and 15 different tumour types, respectively. Moreover, KCNJ14 was discovered to be positively linked with immunological checkpoints and suppressor cells and to have a negative immunophenoscore (IPS). KCNJ14 was linked to tumour mutation burden (TMB), microsatellite instability (MSI), neoantigen (NEO), and programmed death ligand 1 (PD-L1); all four are potential targets for immunotherapies. In addition, a favourable relationship between genomic-instability markers such as heterozygosity (LOH), homologous recombination deficiency (HRD), and mutant-allele tumour heterogeneity (MATH) was demonstrated with KCNJ14. Based on these novel findings, KCNJ14 may be a useful independent prognostic biomarker for a range of cancers.

摘要

癌症是一种全球性的流行病,已经影响了数百万人的生命。发现新的癌症靶点被广泛认为是开发更有效的癌症和其他致命疾病疗法的关键步骤。最近,钾(K)通道已被研究作为癌症治疗的潜在生物靶点。钾内向整流通道亚家族 J 成员 14(KCNJ14)是癌症基因组中研究最少的基因之一。本研究使用多个数据库全面检查了 KCNJ14 基因表达分析、生存、RNA 修饰、免疫治疗参与和癌症干性之间的关系。研究表明,KCNJ14 在多种癌症中失调,包括肺癌、肠道癌、头颈部癌、食道癌和胃癌。此外,KCNJ14 分别与 18 种和 15 种不同肿瘤类型的 RNA 和 DNA 干性有关。此外,还发现 KCNJ14 与免疫检查点和抑制性细胞呈正相关,且免疫表型评分(IPS)为负。KCNJ14 与肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、新抗原(NEO)和程序性死亡配体 1(PD-L1)有关;所有这四个因素都是免疫治疗的潜在靶点。此外,KCNJ14 与基因组不稳定性标志物如杂合性缺失(LOH)、同源重组缺陷(HRD)和突变等位基因肿瘤异质性(MATH)之间存在良好的关系。基于这些新发现,KCNJ14 可能是多种癌症有用的独立预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3936/9916715/ce47a373d86a/ijms-24-02049-g001.jpg

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