HOXC4 is Associated with the Prognosis and Immune Cell Infiltration in the Progression of Prostate Cancer

INTRODUCTION: Members of the Homeobox (HOX) gene family, particularly HOXCs, may be implicated in the development and prognosis of prostate cancer (PCa), but the specific mechanisms remain unclear. METHODS: The clinical and transcriptomic data from TCGA-PRAD and GSE70770 were collected to examine the impact of HOXC family members on progression-free survival (PFS) in PCa. Meanwhile, the mechanisms of HOXC family members in PCa and their relationship with patients' prognosis were systematically investigated by performing survival analysis, enrichment analysis, and COX regression analysis. This study also developed a prognostic model. Additionally, a qPCR assay was conducted to determine the mRNA level of HOXC family members in PCa cells. RESULTS: Upregulated expressions of HOXC4, HOXC5, HOXC12, and HOXC13 in PCa tissues were found to be correlated with a worse prognosis. A prognostic model incorporating HOXC4 expression level, T stage, and Gleason score was constructed, exhibiting excellent performance in predicting 1-, 3-, and 5-year PFS (average AUC > 0.7). Enrichment analysis showed that HOXC4, which was highly expressed in PCa cells, may be involved in the progression and invasion of PCa through pathways such as oxidative phosphorylation, PLK1 signaling, cell cycle, and DNA methylation. Further, ssGSEA showed that HOXC4 may affect immune cell infiltration in PCa tumors. DISCUSSION: HOXC4 was related to immune cell infiltration and pathway activation in PCa and confirmed to be a risk factor for the cancer prognosis. However, the specific molecular mechanisms of HOXC4 in PCa development still require further investigation. CONCLUSION: The HOXC4-based prognostic model may be an effective tool for assessing the prognosis of PCa patients.