Research Paper Volume 11, Issue 20 pp 9209—9219
Overexpression of steroid sulfotransferase genes is associated with worsened prognosis and with immune exclusion in clear cell-renal cell carcinoma
- 1 Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, PR China
Received: April 26, 2019 Accepted: October 21, 2019 Published: October 27, 2019
https://doi.org/10.18632/aging.102392How to Cite
Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.