Purpose:: Hepatocellular carcinoma (HCC) is a significant global health burden. Cancer cells often exhibit an imbalance in intracellular calcium homeostasis. This study aims to explore the relationship between calcium-related genes and the prognosis of HCC, and establish a prognostic model based on calcium-related genes. Methods: This study comprehensively reviewed 392 calcium-related regulators and constructed a Calcium-related Prognostic Risk Score(CPRS) for HCC by means of bootstrap-based univariate Cox, random forest screening, and LASSO analysis. We developed an effective prognostic nomogram for patients with HCC by integrating the CPRS and clinicopathological features. The signature was developed using the TCGA cohort and validated in two independent external cohorts (ICGC and NODE-CHCC). Subsequently, we identified the key genes in CPRS that affect the prognosis of HCC based on SurvSHAP, and further investigated the impact of the key factor CACNA1B on the biological behavior of HCC cells. Results: CPRS was established with 6 calcium-related genes (CSN1S1, S100A9, CACNA1B, FKBP1A, SLC25A24 and SPP1). Our study showed that high CPRS is closely associated with higher histological grade, advanced TNM stage, vascular invasion, poorer progression-free and overall survival (OS) status of HCC, and CPRS can serve as an independent risk factor for the prognosis of HCC patients. The nomogram combining CPRS with TNM stage and patient age significantly improved the accuracy of predicting survival outcomes in HCC patients. Functional experiments revealed that inhibiting CACNA1B expression significantly suppressed cell proliferation, migration, and epithelial-mesenchymal transition signaling in HCC cells. Conclusion: We developed a novel CPRS that can accurately predict the prognosis of HCC. CACNA1B may function as a tumor promotor in HCC progression. Keywords: hepatocellular carcinoma, calcium-related gene, CACNA1B, risk score
Chen et al. (Sun,) studied this question.