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Abstract
Background
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.
Abbreviations
CCT8, Chaperonin containing TCP1 subunit 8; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; TCGA, The Cancer Genome Atlas; GTEx, The Genotype-Tissue Expression; CPTAC, Clinical Proteomic Tumor Analysis Consortium; ICPC, International Cancer Proteogenome Consortium; OS, overall survival; DFS, disease free survival; DSS, disease specific survival; DFI, disease free interval; PFI, progression free interval; Th2, T-helper type 2; Th1, T-helper type 1; CNV, Copy Number Variation; SNV, Single Nucleotide Variants; MSI, microsatellite instability; TMB, tumor mutation burden; ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumours; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Data Sharing Statement
The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.
Ethics Statement
All experiments and methods were performed in accordance with the relevant approved guidelines and regulations, as well as under the approval of the Ethics Committee of the Third Xiangya Hospital of Central South University (No. I 22277).
Acknowledgments
We acknowledge the TCGA, CPTAC, ICPC, GTEx, cBioPortal, UALCAN, TISIDB, Sangerbox and Human Protein Atlas websites for providing their platforms and meaningful datasets. We also sincerely thank the Central Laboratory of the Third Xiangya Hospital and all participants involved in this study.
Author Contributions
All authors made significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; participated in drafting the article or critically revising important intellectual content; agreed to submit the article to the current journal; gave final approval of the version to be published; and agreed to take responsibility for all aspects of the work.
Disclosure
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.