Increased expression of DNAJC7 promotes the progression of hepatocellular carcinoma by influencing the cell cycle and immune microenvironment.

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide owing to the lack of effective and early diagnostic tools and therapeutic approaches. DNAJC7, a member of the DnaJ heat shock family, is crucial in protein folding and stability; however, its specific functions and mechanisms in HCC remain unclear.

Objective: This study aimed to explore the role of DNAJC7 in HCC progression and evaluate its potential clinical significance as a prognostic marker.

Methods: Public databases (TCGA, ICGC, GEO, and TIMER) were used to assess DNAJC7 expression, correlations with clinical parameters, and related signaling pathways. Proliferation, migration, invasion, and cell cycle assays were performed to evaluate the function of DNAJC7 in HCC. Immune infiltration and associations with checkpoint proteins were analyzed using TIMER, and a Gene Set Enrichment Analysis (GSEA) was used to explore enriched pathways.

Results: DNAJC7 expression was higher in HCC tissues than in adjacent normal tissues and was associated with advanced malignancy and poor prognosis, including a lower overall survival, progression-free survival, and disease-free survival. DNAJC7 knockdown resulted in reduced malignant behavior of HCC cells, leading to S-phase cell cycle arrest. Increased DNAJC7 expression was associated with immune cell infiltration and the presence of immunological checkpoint molecules, including CTLA4 and PD-1. GSEA highlighted the activation of key pathways, including WNT signaling and cell cycle regulation.

Conclusion: DNAJC7 regulates tumor cell proliferation, migration, invasion, and immune evasion by acting as an oncogene in HCC. It can serve as a diagnostic and prognostic biomarker and potential treatment target for HCC.