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结直肠癌中染色体框家族成员的预后价值及免疫浸润的综合分析

Comprehensive Analysis of Prognostic Value and Immune Infiltration of Chromobox Family Members in Colorectal Cancer.

作者信息

Li Qingshang, Pan Yi, Cao Zhijun, Zhao Shuliang

机构信息

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, School of Medicine, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Front Oncol. 2020 Sep 4;10:582667. doi: 10.3389/fonc.2020.582667. eCollection 2020.

Abstract

Colorectal cancer (CRC) is one of the common malignant tumors worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and are implicated in the development of multiple cancers by blocking differentiation and promoting proliferation. However, little is known about the function of distinct CBX proteins in colorectal cancer. Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of CBXs in colorectal cancer patients. The expression levels of CBX1/2/3/4/5 and CBX8 were significantly elevated in CRC tissues, whereas the expression levels of CBX6/7 were reduced. CBX3 was significantly associated with the clinical cancer stage and short disease-free survival (DFS) in CRC patients. High mRNA expression of CBX5/6 was associated with short overall survival (OS) in rectal cancer patients. CBX3/5/6 could be potential prognostic biomarkers for the survival of CRC patients. Moreover, the functions of the differentially expressed CBXs were primarily related to the SUMOylation of DNA methylation proteins and chromatin organization and may regulate the pluripotency of stem cells. The expression of CBXs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in colon cancers and rectal cancers. Our study may provide novel insights for the selection of prognostic biomarkers of CBX family in colorectal cancer.

摘要

结直肠癌(CRC)是全球常见的恶性肿瘤之一。染色体框(CBX)家族蛋白是表观遗传调控复合物的重要组成部分,通过阻断分化和促进增殖参与多种癌症的发生发展。然而,关于不同CBX蛋白在结直肠癌中的功能知之甚少。利用Oncomine、基因表达谱交互式分析(GEPIA)、Kaplan-Meier绘图仪、cBioPortal、GeneMANIA和TIMER分析结直肠癌患者中CBXs的差异表达、预后价值、基因改变和免疫细胞浸润情况。CBX1/2/3/4/5和CBX8在CRC组织中的表达水平显著升高,而CBX6/7的表达水平降低。CBX3与CRC患者的临床癌症分期和短无病生存期(DFS)显著相关。CBX5/6的高mRNA表达与直肠癌患者的短总生存期(OS)相关。CBX3/5/6可能是CRC患者生存的潜在预后生物标志物。此外,差异表达的CBXs的功能主要与DNA甲基化蛋白的SUMO化和染色质组织有关,可能调节干细胞的多能性。CBXs的表达与多种免疫细胞的浸润显著相关,包括结肠癌和直肠癌中的六种CD4+T细胞、巨噬细胞、中性粒细胞、B细胞、CD8+T细胞和树突状细胞。我们的研究可能为结直肠癌中CBX家族预后生物标志物的选择提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a90/7498700/b6049a4218aa/fonc-10-582667-g0001.jpg

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