CCT3-related genetic and immune characteristics and its diagnostic and prognostic performances in lung adenocarcinoma

Abstract

Background Chaperonin-containing tailless complex polypeptide 1 (TCP1) subunit 3 (CCT3) is overexpressed in a wide range of cancers and has a connection with poor prognosis. However, its role in lung adenocarcinoma (LUAD), the most common type of non-small cell lung cancer (NSCLC) remained to be elucidated. Methods The Timer and UALCAN databases, Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) data were used to analyze CCT3 expression in LUAD. Both the Wilcoxon rank-sum test and the regression model were used to investigate the connection between clinicopathologic characteristics of LUAD patients and CCT3 expression. The diagnostic efficiency of CCT3 for LUAD was assessed by receiver operating curve, and the prognostic value of CCT3 was determined by Cox regression models, the Kaplan-Meier method and Nomogram prediction. Next, we identified the most related genes with CCT3 via GeneMANIA and String databases, and the association between CCT3 and infiltrated immune cells with single-sample Gene Set Enrichment Analysis (ssGSEA). CCT3-related infiltrating immune cells was investigated by GSEA. Finally, CCT3 roles in cell proliferation and apoptosis of LUAD A549 cells was verified by siRNA (small interfering RNA) mediated knockdown. Results CCT3 was upregulated in LUAD both in mRNA and protein levels. CCT3 overexpression was associated with clinicopathological characteristics including sex, smoking, T- and N-categories, pathological staging, and a poor prognosis of LUAD patients. GeneMANIA and String databases found a set of CCT3-related genes that are connected to the assembly and stability of proteins involved in proteostasis of cytoskeletal filaments, DNA repair and oncogenesis. Furthermore, CCT3 was found to be positively correlated with the infiltrating Th2 cells (r = 0.442, p < 0.01) while negatively correlated with mast cells (r = -0.49, p < 0.01) and immature dendritic cells (iDCs, r = -0.401, p < 0.001) according to ssGSEA analyzes. The pathway analysis based on GSEA method showed that the cell cycle pathway, the protein export pathway, the proteasome pathway and the ribosome pathway are enriched in CCT3 high group, whereas the JAK/STAT pathway, B cell receptor pathway, T cell receptor pathway and toll like receptor pathway were enriched in CCT3 low group. Finally, CCT3 knockdown substantially inhibited proliferation while promoted apoptosis of A549 cells. Conclusion Dysregulation of CCT3 in LUAD is associated with unique genetic and immune properties and has excellent diagnostic and prognostic performance for LUAD.