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人类胶质母细胞瘤中染色体盒家族成员的表达谱及预后价值

Expression profile and prognostic values of Chromobox family members in human glioblastoma.

作者信息

Li Juanni, Xu Zhijie, Zhou Lei, Hu Kuan

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

出版信息

Aging (Albany NY). 2022 Feb 24;14(4):1910-1931. doi: 10.18632/aging.203912.

Abstract

Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Chromobox (CBX) family proteins are essential components of the epigenetic regulatory complex and are involved in the occurrence and development of various cancers. However, the roles of CBX members in GBM is little known. In this analysis, we synthesized several mainstream bioinformatics databases to comprehensively explore the expression profiles, prognostic implications, genetic alterations, immune infiltration, and potential biological functions of the CBXs in GBM, and cell experiments were also conducted to investigate the role of CBX8 in GBM. We found that the elevated mRNA expression of CBX2/3/5/8 and reduced mRNA expression of CBX6/7 were found in GBM. The protein levels of CBX2/3/5/8 were elevated in GBM tissues, whereas the protein levels of CBX6/7 showed no significant difference. The upregulated expression of CBX2/3/8 was found to be both correlated with the tumor grade and recurrent status. The overexpression of CBX3/8 and underexpression of CBX6 mRNA were associated with the poor prognosis. These findings suggested that CBX3 and CBX8 might be useful diagnostic and prognostic biomarkers in GBM. Further cell experiment results supported that CBX8 promoted the proliferation of glioma cells. Moreover, a high genetic alteration rate of CBXs (37%) was found in GBM and to varying degrees. The expression of CBXs was significantly related to the immune cells infiltration. CBX7 methylation level was significantly increased in GBM tissues. Our results may provide novel ideas to find potential prognostic markers and new therapeutic targets among CBX family members in glioblastoma.

摘要

胶质母细胞瘤(GBM)是最常见且致命的原发性恶性脑肿瘤。染色体盒(CBX)家族蛋白是表观遗传调控复合物的重要组成部分,参与多种癌症的发生和发展。然而,CBX成员在GBM中的作用鲜为人知。在本分析中,我们整合了多个主流生物信息学数据库,全面探究CBXs在GBM中的表达谱、预后意义、基因改变、免疫浸润及潜在生物学功能,并进行细胞实验以研究CBX8在GBM中的作用。我们发现,GBM中CBX2/3/5/8的mRNA表达升高,CBX6/7的mRNA表达降低。GBM组织中CBX2/3/5/8的蛋白水平升高,而CBX6/7的蛋白水平无显著差异。发现CBX2/3/8的表达上调与肿瘤分级和复发状态均相关。CBX3/8的过表达和CBX6 mRNA的低表达与预后不良相关。这些发现表明,CBX3和CBX8可能是GBM有用的诊断和预后生物标志物。进一步的细胞实验结果支持CBX8促进胶质瘤细胞增殖。此外,在GBM中发现CBXs有较高的基因改变率(37%),且程度各异。CBXs的表达与免疫细胞浸润显著相关。GBM组织中CBX7甲基化水平显著升高。我们的结果可能为在胶质母细胞瘤的CBX家族成员中寻找潜在的预后标志物和新的治疗靶点提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3530/8908931/163a3f4fe569/aging-14-203912-g002.jpg

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