Hepatocellular carcinoma (HCC) is the most common type of primary liver malignancy, with increased mortality and morbidity. Accumulating evidence suggested that 40S ribosomal protein S24 (RPS24) is related to malignant outcomes and progression. However, the role of RPS24 remains unclear in HCC. The mRNA and protein expression pattern of RPS24 in HCC was explored and confirmed based on the bioinformatics analysis and histological examination. The correlation between RPS24 expression and clinicopathological features, diagnostic value, prognosis, methylation status, and survival were evaluated. Then, we divided the HCC cohort into two groups based on the expression of RPS24, and performed the functional enrichment and immune cells infiltration analysis of RPS24. Furthermore, in vivo and in vitro experiments were performed to investigate the effect of RPS24 on HCC cells. RPS24 was observed to be elevated in HCC samples. RPS24 overexpression or RPS24 promoter methylation contributed to an unfavorable prognosis for HCC patients. The genes in the high RPS24 expression group were mainly enriched in DNA replication, cell cycle E2F targets, and the G2M checkpoint pathway. Moreover, the expression level of RPS24 was significantly related to immune infiltration and immunotherapy response. Our experiments also demonstrated that RPS24 knockdown suppressed the growth of HCC cells and tumor proliferation of the xenograft model. Therefore, RPS24 can be a potential adverse biomarker of HCC prognosis acting through facilitating cell proliferation and the formation of an immunosuppressive microenvironment in HCC. Targeting RPS24 may offer a promising therapeutic option for HCC management.

Coagulation factor family genes play a pivotal role in tumor progression and immune modulation, but their relationship with tumor microenvironment and immunotherapy response in gastric cancer remains unclear. This study utilized single-cell and The Cancer Genome Atlas datasets to investigate the clinical and immune relevance of coagulation factor family genes in gastric cancer. Based on coagulation factor family genes, a risk score was constructed. The high-risk group was found to have a worse prognosis and exhibited an immunosuppressive state. Coagulation factor V (F5) emerged as a central gene, correlating negatively with immune cell recruitment and cytotoxic activity within the tumor immune cycle. In vitro knockdown experiments and in vivo 615 mouse liver metastasis models showed that F5 enhances metastasis and reduces CD8+ T cell infiltration. Immunohistochemistry (n = 64) and flow cytometry (n = 31) further confirmed F5 immunomodulatory effects. Among 37 patients receiving neoadjuvant immunotherapy, low F5 expression was associated with improved response. Finally, Gastrodin was identified via virtual screening and molecular dynamics as a potential small-molecule inhibitor of F5. These findings indicate that coagulation factor family genes, particularly F5, promote gastric cancer progression and immune evasion, and that targeting F5 may enhance immunotherapeutic outcomes.