Multi-Omics Analysis and Verification of the Oncogenic Value of CCT8 in Pan-Cancers

Lian Gong,1 Ming Zhong,2 Kai Gong,3 Zhanwang Wang,1 Yong Zhong,4 Yi Jin,1 Haotian Chen,1 Panpan Tai,1 Xinyu Chen,1 Aiyan Chen,1 Ke Cao1 1Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Clinical Medicine, Xiangnan University, Chenzhou, People’s Republic of China; 4Department of Clinical Medicine, Hubei Enshi College, Enshi, People’s Republic of ChinaCorrespondence: Ke Cao, Email csucaoke@163.comBackground: Chaperonin-containing TCP1 subunit 8 (CCT8) has been proved to be involved in the occurrence and development of some cancers. However, no study has reported the potential role of CCT8 in a pan-cancer manner.Methods: TIMER2.0, GEPIA2, UALCAN and Sangerbox were used to explore the expression, prognosis and methylation of CCT8. We used cBioPortal, TISIDB, SangerBox, TIMER2.0 and TISMO to investigate the genetic alteration of CCT8 and the relationship of CCT8 with molecular subtype, immune subtype, immune infiltration and immunotherapy response. CCT8-related genes were screened out through GEPIA and STRING for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CCK-8, the colony formation assay, the wound healing assay and the Transwell assay were performed to explore the influence of CCT8 on proliferation and migration.Results: CCT8 was highly expressed in most cancers with a poor prognosis. The expression level of CCT8, which was affected by the promoter region methylation and genetic alteration, was related to the molecular and immune subtype of cancers. Interestingly, CCT8 was positively associated with the activated CD4 T cells and type 2 T-helper cells. CCT8 played a vital role in the cell cycle and RNA transport of cancers, and it significantly inhibited the proliferation and migration of lung adenocarcinoma cells when it was knocked down.Conclusion: CCT8 plays an indispensable role in promoting the proliferation and migration of many cancers. CCT8 might be a biomarker of T-helper type 2 (Th2) cell infiltration and a promising therapeutic target for T-helper type 1(Th1)/Th2 imbalance.Keywords: CCT8, survival, immune infiltration, biomarker, pan-cancer