Prognostic Value, Immune Landscape, and Drug Response ofHOGA1 in Clear Cell Renal Cell Carcinoma

Introduction: HOGA1 is expressed mainly in the liver and kidney, and mutations of this gene were reported to be the cause of primary hyperoxaluria type III. In malignant tumors, HOGA1 has been reported to function as a suppressor in pancreatic cancer. But its role in renal cell carcinoma remained undetermined. This study aims to explore the expression, prognostic value, immune landscape, and drug response associations of HOGA1 in clear cell renal cell carcinoma(ccRCC). Methods: The Immunohistochemistry (IHC) was carried out to illuminate the protein expression of HOGA1 in ccRCC and normal renal tissues. Several publicly available databases and bioinformatics analyses were performed to detect the role of HOGA1 in ccRCC. Results: Bioinformatics analysis and IHC indicated that HOGA1 expression was obviously reduced in ccRCCs compared with normal renal tissues. And Multivariate analysis clarified that HOGA1 mRNA expression was an independent prognostic factor in ccRCC. Patients with lower HOGA1 expression levels had a worse prognosis. Additionally, Enrichment analysis showed that HOGA1-associated genes were mainly enriched in drug metabolism in ccRCC. HOGA1 showed weak but statistically significant negative correlations with the IC50 value of Afatinib, Erlotinib, Rapamycin, and Sorafenib. In addition, HOGA1 expression was found to be correlated with immune infiltration and immune evasion. Discussion: Clear cell renal cell carcinoma (ccRCC) remains a significant clinical challenge due to its aggressive nature and limited therapeutic options. Our analysis highlights HOGA1 as a potential tumor suppressor in ccRCC, with its reduced expression associated with poorer prognosis. Using bioinformatics tools, we revealed that lower HOGA1 expression correlates with increased immune evasion and metabolic dysregulation within the tumor microenvironment (TME), contributing to ccRCC progression. Specifically, we found that HOGA1 loss may enhance the recruitment of macrophages, myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs), which play key roles in immune suppression and tumor survival. Moreover, HOGA1 expression was positively correlated with improved sensitivity to several chemotherapy drugs, suggesting its potential as a therapeutic target. These findings underscore the importance of HOGA1 in regulating both metabolic and immune landscapes in ccRCC and highlight its role as a novel prognostic biomarker. However, further validation through independent clinical cohorts and mechanistic studies, including in vitro and in vivo experiments, is needed to confirm these observations and explore the therapeutic potential of restoring HOGA1 function in ccRCC treatment. Conclusion: Overall, HOGA1 may serve as a suppressor in ccRCC. Downregulation of HOGA1 may facilitate the malignant progression of ccRCC by regulating TME and disrupting the metabolic balance. Consequently, HOGA1 may serve as a potential biomarker in ccRCC, though its therapeutic implications remain to be validated