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.
Highlights
According to the “global cancer statistics” released by the World Health Organization (WHO) in 2015, approximately 1.15 million new cases of breast cancer are diagnosed every year and it accounts for 23% of all female malignancies; there are approximately 410,000 deaths every year, accounting for 14% of deaths due to cancer in women worldwide [1]
Containing TCP1 Subunit 2 (CCT2) expression was significantly higher in BLCA, BRCA, CHOL (Cholangiocarcinoma), COAD, ESCA (Esophageal carcinoma), HNSC, KIRP (Kidney renal papillary cell carcinoma), LIHC, LUAD, LUSC (Lung squamous cell carcinoma), PRAD (Prostate adenocarcinoma), READ (Rectum adenocarcinoma), STAD, and UCEC (Uterine Corpus Endometrial Carcinoma) when compared with adjacent normal tissues
CCT2 expression was significantly lower in only two types of cancers, that were, KICH (Kidney Chromophobe) and KIRC (Kidney renal clear cell carcinoma)
Summary
According to the “global cancer statistics” released by the World Health Organization (WHO) in 2015, approximately 1.15 million new cases of breast cancer are diagnosed every year and it accounts for 23% of all female malignancies; there are approximately 410,000 deaths every year, accounting for 14% of deaths due to cancer in women worldwide [1]. The hardened armors of cancer such as genomic instability, uncontrolled proliferation, metastasis, and so on make it a well-equipped army to fight against our various therapeutics [2, 3], it does have a soft spot: its dependency on major cellular processes like transcription, translation, splicing, protein degradation, and protein-folding [4]. During this significant process, proteostasis network (PN), contributing a lot to keep proteome balanced, plays an important role in maintaining native function of proteins and guaranteeing the health of cell and organism. Cancer cells become more highly addicted to molecular chaperones since there are more imbalances caused by overexpression of oncogenes and chromosomal abnormalities [6]
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