Expression patterns and clinical implications of chaperonin subunit 3 mRNA and protein in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a prevalent head and neck malignancy with suboptimal survival rates due to late detection and therapeutic resistance. AIM: To investigate chaperonin-containing TCP1 subunit 3 (CCT3) expression and its clinical implications, and its effects on LSCC cell growth. METHODS: Systematic data on CCT3 mRNA expression were collected from biomedical databases, and integrated further based on the standardized mean difference and the summary receiver operating characteristic curve. Single-cell RNA-seq data were mined to validate the expression level of CCT3 mRNA. In-house immunohistochemistry was performed to explore the CCT3 protein levels of clinical LSCC samples and their relationship with clinical parameters. The growth function of LSCC cell was analyzed using CRISPR knockout screening. CCT3-related signaling pathway analyses were conducted using gene set enrichment analysis. Protein-protein interaction network construction was performed to identify hub genes. RESULTS: CCT3 mRNA was significantly overexpressed in 269 LSCC tissues cases across multiple independent datasets (standardized mean difference = 32, area under the curve = 0.93); At the translational level, the in-house immunohistochemical analysis further demonstrated the consistent upregulation of CCT3 protein in 88 cases of LSCC samples (58 non-LSCC samples vs 30 LSCC samples, P = 1.4e-14). Analysis of clinical parameters showed no significant differences among subgroup. Functional characterization with clustered regularly interspaced short palindromic repeats--mediated gene knockout revealed that depletion of CCT3 potently suppressed LSCC cell viability in vitro. Gene set enrichment analysis indicated that CCT3 was markedly associated with several key oncogenic pathways, including extracellular matrix receptor interaction and cell cycle regulation pathways. CONCLUSION: CCT3 upregulation in LSCC may influence cellular growth by regulating related pathways, indicating its potential as a biomarker and therapeutic target for LSCC.