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CCT2表达与预后的分子及临床特征:乳腺癌的大规模转录组图谱

Molecular and Clinical Characterization of CCT2 Expression and Prognosis Large-Scale Transcriptome Profile of Breast Cancer.

作者信息

Liu Qiang, Qi Yihang, Kong Xiangyi, Wang Xiangyu, Zhang Wenxiang, Zhai Jie, Yang Yazhe, Fang Yi, Wang Jing

机构信息

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, United States.

出版信息

Front Oncol. 2021 Apr 2;11:614497. doi: 10.3389/fonc.2021.614497. eCollection 2021.

Abstract

Molecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperone CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2). CCT2 is a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). Through the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2,994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer. We found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype. In summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.

摘要

分子伴侣在调节各种细胞过程和恶性转化中发挥着重要作用。据报道,分子伴侣CCT/TRiC复合体的一些亚基的表达与癌症发展和患者生存率相关。然而,关于含TCP1亚基2的伴侣蛋白(CCT2)的表达及其预后意义却知之甚少。CCT2是一个编码分子伴侣的基因,它是含TCP1复合体(CCT)的成员,也被称为TCP1环复合体(TRiC)。通过癌症基因组图谱(TCGA)和国际乳腺癌分子分类联盟(METABRIC)数据库,我们系统地回顾了总共2994例有转录组数据的病例,并通过基因本体论和KEGG分析对CCT2进行了功能注释。进行单因素和多因素生存分析以研究CCT2在乳腺癌中的预后价值。我们发现CCT2在各种肿瘤中显著上调。在乳腺癌中,CCT2表达在HER2阳性(HER2+)组和恶性程度更高的组中显著上调。此外,我们研究了CCT2与其他CCT成员之间的相关性。有趣的是,几乎所有CCT的表达都相互呈正相关,但CCT6B除外。生存分析表明,CCT2过表达与乳腺癌患者的预后较差独立相关,尤其是在腔面A型亚型中。总之,我们的结果表明CCT2可能参与调节细胞周期途径,并独立预测乳腺癌患者的预后较差。这些发现可能会扩展对潜在的抗CCT2治疗的理解。据我们所知,这是关于CCT2在乳腺癌中的表达模式及其预后价值的最大且最全面的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf9/8050343/9d35ff5a341b/fonc-11-614497-g001.jpg

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