Chaperonins in Hepatocellular Carcinoma: Unveiling Their Role in Tumor Proliferation and Immune Modulation Through Multiomics Analysis.

Background: Chaperonins are crucial regulators of tumor biology by controlling the stability and function of oncogenic and tumor-suppressor proteins, influencing various tumorigenic signaling pathways. Although chaperonins have been widely discussed in various cancers, including hepatocellular carcinoma (HCC), the complex mechanisms by which they contribute to HCC progression remain insufficiently explored and require further investigation. Methods: Based on data from public databases, we screened chaperonin members from the Human Genome Organisation (HUGO) Gene Nomenclature Committee (HGNC) database. The screened genes were subjected to differential expression analysis, survival analysis, clinical correlation, and univariate Cox regression. Results were validated using single-cell RNA (scRNA) and spatial transcriptomics (ST) data. Functional enrichment and in vitro assays were also performed. Results: Chaperonins, particularly CCT6B, were significantly overexpressed in HCC tissues, with higher expression correlating with poor prognosis in HCC patients. CCT6B was found to be involved in cell cycle regulation, promoting tumor cell proliferation. Additionally, CCT6B contributed to M2 macrophage infiltration, potentially through CCL20 signaling. Moreover, the expression levels of chaperonins were associated with β-catenin activation in malignant cells, suggesting their collective involvement in HCC progression. Conclusion: This study elucidates a substantial association between dysregulated chaperonin expression profiles and genomic aberrations in pan-cancer, underscoring the functional significance of these chaperonin molecules in understanding cell cycle regulation. Systematic characterization of chaperonin-mediated regulatory networks enhances mechanistic insights into oncogenic processes and aberrant cellular proliferation, thereby informing the rational design of precision therapeutic interventions.