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

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.

Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer

“…Our analysis of Kaplan–Meier survival of tumors by TCGA data displayed that a high CCT2 expression was related to poor prognosis in ACC, GBMLGG, LIHC, LUAD, MESO, SARC, and THYM. Similarly, one study reported that, in breast cancer, a high expression of CCT2 predicted its poor prognosis ( 15 ). In gallbladder cancer, it was shown by multifactorial analysis that a positive CCT2 expression was negatively correlated with low postoperative patient survival and positively correlated with high mortality ( 10 ).…”

“…In other studies, the expression levels of TRiC subunits TCP1, CCT2, CCT 3, CCT 4, CCT 5, CCT 6A, CCT 7, and CCT 8 were significantly upregulated in HCC ( 14 ). PAAD, READ, STAD, and UCEC are significantly upregulated in CCT2 expression than in adjacent normal tissues ( 9 , 15 ).…”

Proteomic changes associated with maternal dietary low ω6:ω3 ratio in piglets supplemented with seaweed Part II: Ileum proteomes

“…The increased abundance of protein RPSA in LR versus CR ileum in this study may relate to the positive regulation of the protein synthesis process [41], thereby contributing to immune response activation [40]. Chaperonincontaining T-complex protein 1 (CCT) is a macromolecular protein folding complex that consists of eight subunit proteins (CCT1-8) [43] relating to cell cycling dysregulation and leading to uncontrolled proliferation [44]. The subunit beta (CCT2) may drive cell division and attract proliferative factors in humans, affecting crucial survival and growth components [44].…”

Revisiting the chaperonin T‐complex protein‐1 ring complex in human health and disease: A proteostasis modulator and beyond

“…KEGG analysis of breast cancer cells revealed enrichment of CCT2-related genes in the cell cycle and p53 signalling pathways. 122 However, the exact relationship between CCT2 and p53 in breast cancer is still unknown. Interestingly, in colorectal cancer (CRC) cells, overexpression of CCT8 significantly increases cell proliferation by preventing wild-type p53 from being transported into the nucleus, contributing to p53 inactivation.…”