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Prognostic Power of a Chaperonin Containing TCP-1 Subunit Genes Panel for Hepatocellular Carcinoma.

ABSTRACT: Chaperonin containing TCP-1 (T-complex protein 1) (CCT) is a large molecular weight complex that contains nine subunits (TCP1, CCT2, CCT3, CCT4, CCT5, CCT6A, CCT6B, CCT7, CCT8). This study aimed to reveal key genes which encode CCT subunits for prognosis and establish prognostic gene signatures based on CCT subunit genes. The data was downloaded from The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus. CCT subunit gene expression levels between tumor and normal tissues were compared. Corresponding Kaplan-Meier analysis displayed a distinct separation in the overall survival of CCT subunit genes. Correlation analysis, protein-protein interaction network, Gene Ontology analysis, immune cells infiltration analysis, and transcription factor network were performed. A nomogram was constructed for the prediction of prognosis. Based on multivariate Cox regression analysis and shrinkage and selection method for linear regression model, a three-gene signature comprising CCT4, CCT6A, and CCT6B was constructed in the training set and significantly associated with prognosis as an independent prognostic factor. The prognostic value of the signature was then validated in the validation and testing set. Nomogram including the signature showed some clinical benefit for overall survival prediction. In all, we built a novel three-gene signature and nomogram from CCT subunit genes to predict the prognosis of hepatocellular carcinoma, which may support the medical decision for HCC therapy.

SUBMITTER: Li W

PROVIDER: S-EPMC8061729 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Chaperonin containing TCP1 (CCT/TRiC) is a multi-subunit protein folding complex that enables the cancer phenotype to emerge from the mutational landscape that drives oncogenesis. We and others linked increased expression of CCT subunits to advanced tumor stage and invasiveness that inversely correlates with cancer patient outcomes. In this study, we examined the expression of the second CCT subunit, CCT2, using genomic databases of adult and pediatric tumors and normal tissues, and found that it was highly expressed in pediatric cancers, showing a significant difference compared to normal tissues. Histologic staining confirmed that CCT subunits are highly expressed in tumor tissues, which was exemplified in neuroblastoma. Using two neuroblastoma cells, MYCN-amplified, IMR-32 cells, and non-amplified, SK-N-AS cells, we assessed baseline levels for CCT subunits and found expressions comparable to the highly invasive triple-negative breast cancer (TNBC) cell line, MDA-MB-231. Exogenous expression of CCT2 in both SK-N-AS and IMR-32 cells resulted in morphological changes, such as larger cell size and increased adherence, with significant increases in the CCT substrates, actin, and tubulin, as well as increased migration. Depletion of CCT2 reversed these effects and reduced cell viability. We evaluated CCT as a therapeutic target in IMR-32 cells by testing a novel peptide CCT inhibitor, CT20p. Treatment with CT20p induced cell death in these neuroblastoma cells. The use of CCT2 as a biological indicator for detection of neuroblastoma cells shed in blood was examined by spiking IMR-32 cells into human blood and using an anti-CCT2 antibody for the identification of spiked cancer cells with the CellSearch system. Results showed that using CCT2 for the detection of neuroblastoma cells in blood was more effective than the conventional approach of using epithelial markers like cytokeratins. CCT2 plays an essential role in promoting the invasive capacity of neuroblastoma cells and thus offers the potential to act as a molecular target in the development of novel therapeutics and diagnostics for pediatric cancers.

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Prognostic Power of a Chaperonin Containing TCP-1 Subunit Genes Panel for Hepatocellular Carcinoma.

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