HK3: A potential prognostic biomarker with metastasis inhibition capabilities in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) stands as one of the prevalent malignant tumors worldwide. The effectiveness of immunotherapy frequently depends on the intricate dynamics of immunomodulation within the tumor microenvironment (TME). The current study aims to identify prognostically relevant genes and their functional roles in HCC. This is achieved by utilizing immune scores and mutations as the basis, through the application of bioinformatics and molecular biological analysis.

Differentially expressed genes (DEGs) analysis was conducted using the "clusterProfiler" package for functional enrichment. Cox regression analysis and LASSO regression analysis were performed for prognostic gene screening. Kaplan-Meier curve were further utilized to verify the prognostic value of these genes. The relationship between selected genes and immune cells was analyzed using ssGSEA algorithm and TIMER. The HK3 expression in HCC cells was tested by Western blot. Additionally, wound healing and transwell assays were utilized to detect the impact of HK3 on HCC metastasis.

Patients who had higher ESTIMATE, stromal, and immune scores exhibited more favorable overall survival rates. There are 17 genes that overlap among the DEGs related to the immune-stromal-ESTIMATE scores, mutated genes, and DEGs in HCC tissues compared to normal tissues. Among the DEGs, three genes (STAB1, COL15A1 and HK3) emerged with the most profound association concerning survival outcomes. Notably, the HK3 genes displayed a pronounced correlation with immune infiltration. Concurrently, diminished expression levels of HK3 were observed in HCC tissues and upregulation of HK3 resulted in a significant reduction in HCC cell metastasis in vitro and in vivo.

HK3 emerges as a novel prognostic biomarker for HCC, exerting regulatory influence over cellular proliferation, metastasis, and invasiveness. These findings indicate that HK3 holds promise as a potential candidate for treatment and prognosis of HCC.