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CENPK基因的泛癌研究:临床意义与肿瘤免疫

Pan-cancer investigation of CENPK gene: clinical significance and oncogenic immunology.

作者信息

Zeng Hanqian, Shen Yanyan, Hirachan Suzita, Bhandari Adheesh, Zhang Xiangjian

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang Province, People's Republic of China.

Department of Breast Surgery, The Second Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang Province, People's Republic of China.

出版信息

Am J Transl Res. 2021 Dec 15;13(12):13336-13355. eCollection 2021.

Abstract

Many studies have confirmed that the CENPK gene regulates the progression of cancers, but its specific molecular mechanism remains unidentified, as does its significance in the analysis of human cancers. We specify a comprehensive genomic architecture of the CENPK gene associated with the tumor immune microenvironment and its clinical relevance across a broad spectrum of solid tumors. Statistics from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) of over 30 solid tumors were examined. CENPK was expressed differentially in several cancers and is significantly associated in survival outcomes, with higher CENPK signifying a worse prognosis for ACC, KICH, KIRC, KIRP, LGG, LIHC, LUAD, MESO, and SARC. We further examined its clinical relevance with tumor immunogenic features. The expression level of CENPK was not only strongly linked to the tumor infiltration, such as tumor-infiltrating immune cells and immune scores but also linked to microsatellite instability and tumor mutation burden in diverse cancers (P<0.05). I mmune markers such as TNFRSF14 and VSIR were highly expressed on over 20 kinds of human cancer and mismatch repair genes like MLH1, MSH2, MSH6, and PMS2 were positively related with CENPK expression. Moreover, the methyltransferases and functional pathways also seem to have a relationship with the CENPK. CENPK is expected to be a guiding marker gene for clinical prognosis and tumor personalized immunotherapy.

摘要

许多研究已证实CENPK基因调控癌症进展,但其具体分子机制仍不明晰,其在人类癌症分析中的意义亦如此。我们明确了与肿瘤免疫微环境相关的CENPK基因的全面基因组结构及其在广泛实体瘤中的临床相关性。研究了来自癌症基因组图谱(TCGA)和癌症细胞系百科全书(CCLE)的30多种实体瘤的统计数据。CENPK在多种癌症中表达存在差异,且与生存结果显著相关,CENPK水平越高表明肾上腺皮质癌(ACC)、肾嫌色细胞癌(KICH)、肾透明细胞癌(KIRC)、肾乳头状细胞癌(KIRP)、脑胶质瘤(LGG)、肝内胆管癌(LIHC)、肺腺癌(LUAD)、间皮瘤(MESO)和肉瘤(SARC)的预后越差。我们进一步研究了其与肿瘤免疫原性特征的临床相关性。CENPK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评分,还与多种癌症中的微卫星不稳定性和肿瘤突变负荷相关(P<0.05)。肿瘤坏死因子受体超家族成员(TNFRSF14)和病毒特异性免疫受体(VSIR)等免疫标志物在20多种人类癌症中高表达,错配修复基因如错配修复蛋白1(MLH1)、错配修复蛋白2(MSH2)、错配修复蛋白6(MSH6)和错配修复蛋白2(PMS2)与CENPK表达呈正相关。此外,甲基转移酶和功能通路似乎也与CENPK有关。CENPK有望成为临床预后和肿瘤个性化免疫治疗的指导标记基因。

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Pan-cancer whole-genome analyses of metastatic solid tumours.泛癌种实体瘤全基因组分析。
Nature. 2019 Nov;575(7781):210-216. doi: 10.1038/s41586-019-1689-y. Epub 2019 Oct 23.

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