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皮肤黑色素瘤中与肿瘤发生和预后相关的免疫相关生物标志物的鉴定

Identification of immune-related biomarkers associated with tumorigenesis and prognosis in skin cutaneous melanoma.

作者信息

Ji Zhong-Hao, Ren Wen-Zhi, Yang Shuo, Wang Dong-Xu, Jiang Zi-Ping, Lin Chao, Jin Ye, Tian Wen-Tai

机构信息

Department of Hand and Foot Surgery, First Hospital Jilin University Changchun, Jilin, China.

Department of Laboratory Animals, College of Animal Sciences, Jilin University Changchun, Jilin, China.

出版信息

Am J Cancer Res. 2022 Apr 15;12(4):1727-1739. eCollection 2022.

Abstract

Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive forms of cancer. Investigating the mechanisms of carcinogenesis further could lead to the discovery of prognostic biomarkers that could be used to guide cancer treatment. In this study, we conducted integrative bioinformatics analyses of TCGA database, STRING, cBioPortal, TRRUST, The Human Protein Atlas, and DGIdb to determine which hub genes contributed to tumor progression and the cancer-associated immunology of SKCM. The results show that immune-related 873 differential genes grouped SKCM samples into subtypes. The initial results showed that the optimal number of clusters was two subgroups. Further analysis showed that there were significant differences in survival rate and immune infiltration level between the two subgroups. Subsequently, obtaining the different genes between groups, construct PPI to screen 6 hub genes (HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, HLA-DRB5). In total, 6 MHC class II molecules were significantly related to overall survival. We then analyzed the expression of these genes along with their mutation landscapes, transcription factor regulation, and drug regulatory networks. In summary, our study identified 6 MHC class II molecules (HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, HLA-DRB5) as important biomarkers in the occurrence and progression of SKCM tumors. Their expression levels are closely related to prognosis and immune infiltration and can help us better understand the tumorigenesis of SKCM.

摘要

皮肤黑色素瘤(SKCM)是最恶性和侵袭性最强的癌症形式之一。进一步研究其致癌机制可能会发现可用于指导癌症治疗的预后生物标志物。在本研究中,我们对TCGA数据库、STRING、cBioPortal、TRRUST、人类蛋白质图谱和DGIdb进行了综合生物信息学分析,以确定哪些枢纽基因促成了SKCM的肿瘤进展和癌症相关免疫学。结果表明,873个免疫相关差异基因将SKCM样本分为不同亚型。初步结果显示,最佳聚类数为两个亚组。进一步分析表明,两个亚组之间的生存率和免疫浸润水平存在显著差异。随后,获取组间差异基因,构建蛋白质-蛋白质相互作用网络(PPI)以筛选出6个枢纽基因(HLA-DPA1、HLA-DPB1、HLA-DQA1、HLA-DRA、HLA-DRB1、HLA-DRB5)。总共有6种II类主要组织相容性复合体分子与总生存期显著相关。然后,我们分析了这些基因的表达及其突变图谱、转录因子调控和药物调控网络。总之,我们的研究确定6种II类主要组织相容性复合体分子(HLA-DPA1、HLA-DPB1、HLA-DQA1、HLA-DRA、HLA-DRB1、HLA-DRB5)是SKCM肿瘤发生和进展中的重要生物标志物。它们的表达水平与预后和免疫浸润密切相关,有助于我们更好地理解SKCM的肿瘤发生机制。

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