Exploring the role of CCT7 in prognosis, cell cycle regulation, and immune microenvironment remodeling of lung adenocarcinoma based on multi-omics datasets and functional experiments

Abstract

Background

Lung adenocarcinoma (LUAD) represents one of the most prevalent and lethal malignancies, accounting for a significant proportion of cancer-associated deaths worldwide. The persistently unfavorable clinical outcomes associated with this disease highlight the critical demand for identifying innovative molecular markers and developing targeted therapeutic interventions. The chaperonin-containing TCP-1 subunit 7 (CCT7) has been implicated in carcinogenesis across malignancies, but its specific role in LUAD pathogenesis and clinical utility remains poorly defined.

Methods

We evaluated CCT7 expression in LUAD using TCGA, GSE118370, CPTAC, and HPA datasets, correlating it with clinicopathological features and survival outcomes. Functional assays (cell cycle analysis, proliferation, colony formation) in A549/H1229 cells, single-cell RNA sequencing, miRNA regulatory studies, and drug sensitivity analyses (GDSC/CTRP) were performed to explore its mechanisms and clinical potential.

Results

CCT7 was significantly upregulated in LUAD at both mRNA and protein levels, associating with advanced pathological stages, lymph node metastasis, and poor survival (AUC > 0.5 for 1-, 3-, and 5-year outcomes). It promoted LUAD proliferation via the FOXM1-POLE2 pathway, with knockdown inducing M-phase arrest. CCT7 shaped an immunosuppressive tumor microenvironment (reduced CD8+ T cells, elevated Th2 cells) and enhanced crosstalk between tumor cells and stromal/immune populations. Hsa-miR-145-5p negatively regulated CCT7. High CCT7 correlated with increased tumor mutational burden and sensitivity to FK866/Vorinostat, but resistance to Erlotinib.

Conclusion

CCT7 acts as an independent prognostic biomarker in LUAD, driving progression through cell cycle regulation, microenvironment remodeling, and immune modulation. It holds promise as a therapeutic target and guide for personalized LUAD treatment.