Clinical and prognostic value of chaperonin containing T-complex 1 subunit 3 in hepatocellular carcinoma: A Study based on microarray and RNA-sequencing with 4272 cases.

Liver cancer is one of the few tumors with a steadily increasing morbidity and mortality; hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. We combined the expression profiles of Chaperonin Containing T-complex 1 Subunit 3 (CCT3) in HCC tissues based on microarray and RNA-sequencing data. The CCT3 expression levels were extracted and examined based on 421 samples from The Cancer Genome Atlas (TCGA) (HCC, n = 371; non-HCC, n = 50) and 3851 samples from 31 microarray or RNA-sequencing datasets (HCC, n = 1975; non-tumor = 1876). We used a variety of meta-analytic methods, including SMD forest maps, sensitivity analysis, subgroup analysis and sROC curves, to confirm the final results. Meanwhile, database-derived immunohistochemistry data was used for validation. We also further explained the potential mechanism of CCT3 in HCC through signal pathway analyses and PPI network construction with the CCT3 co-expressed genes. The mRNA and protein expression of CCT3 in HCC tissues were higher than in non-HCC tissues. The expression of CCT3 differed between groups when grouped according to clinicopathological parameters, such as race, family history, and histological grade. The results of standardised mean difference (SMD) forest map and summary receiver operating characteristic (sROC) curve revealed that CCT3 was highly expressed in HCC tissues and had a high ability to distinguish between cancer tissues and non-cancer tissues. The main form of CCT3 gene alteration in HCC was mRNA up-regulation and amplification (23%), and the most common mutation type was missense. The mRNA expression of CCT3 in HCC was negatively correlated with DNA methylation. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, CCT3 can influence HCC occurrence and development through cell cycle and DNA replication pathways. In summary, this study carries out the staging and prognostic analysis of HCC. It suggests that CCT3 might play an important part in the tumorigenesis and progression of HCC and may have a certain prognostic value in HCC. Moreover, CCT3 might represent a promising biomarker for HCC.