Overexpression of steroid sulfotransferase genes is associated with worsened prognosis and with immune exclusion in clear cell-renal cell carcinoma.

AIM: Steroid sulfotransferase (SULT) plays physiological roles but its role in clear cell-renal cell carcinoma (ccRCC) remains unclear. We therefore investigated genetic alteration of steroid SULT genes in ccRCC. RESULTS: Overexpression of any of SULT genes occurred in ~8% of ccRCC patients. Overexpression of steroid SULT genes was associated with worsened prognosis. Steroid SULT gene-upregulated ccRCC cases showed mutual exclusivity with mutations of VHL, SETD2 and PBRM1, and with focal deletions of 3p and 9p, respectively. Expressions of SULT genes were negatively correlated with that of VHL, SETD2 and PBRM1, respectively. While no cancer-intrinsic pathway was enriched, immune signatures were significantly enriched in SULT gene-overexpressed cases, resulting in significantly fewer infiltration of lymphocytes. Targeting SULT1B1 significantly inhibited growth of ccRCC cells. CONCLUSION: Steroid SULT genes were associated with worsened prognosis and with immune exclusion in ccRCC. METHODS: In silico reproduction of TGGA and GTEx datasets was performed. Data were processed comprehensively using the platforms of cBioPotal, GEPIA, Human Protein Atlas, TIMER, respectively. Functional annotation was analyzed using platforms of NET-GE and GSEA, respectively. In vitro assays were performed for validation.