Patterns of Expression of H2S-Producing Enzyme in Human Renal Cell Carcinoma Specimens: Potential Avenue for Future Therapeutics

Background: Renal cell carcinoma (RCC) is the most common cancer of the kidney. The most common histotype is clear-cell (cc) RCC. Hydrogen sulfide (H2S) is an angiogenic and anti-apoptotic gasotransmitter that is elevated under pseudohypoxic conditions. H2S is endogenously produced by three enzymes: Cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST). Seeing as increased expression of these enzymes has been observed in other human cancer types, this study aimed to quantify H2S-producing enzyme expression in human RCC samples and evaluate whether it correlated with clinical outcomes. Patients and Methods: Eighty-eight human kidney tissue specimens, with healthy and cancerous tissue components, were immunohistochemically stained for CSE, CBS, and MPST. The mean pixel intensity of positively stained areas was quantified. A retrospective analysis was conducted to obtain patient demographics, rates of metastasis/recurrence, and prognostic characteristics. Statistical correlations between enzyme expressions and subsequent patient outcomes were evaluated. Results: There was significantly greater expression of CSE, CBS, and MPST in cc-RCC compared to paired healthy tissue (p<0.0001). The difference in expression of CSE in cancerous versus normal tissue was significantly greater than that for CBS and MPST (p<0.000I and p<0.01, respectively). Enzyme expression patterns in cancerous versus normal tissue did not correlate with nuclear grade, stage, histological type or cancer recurrence/metastasis. Conclusion: To our knowledge, this is the first report of the differential increase in expression of CSE, CBS, and MPST in human RCC. Although these patterns do not appear to correlate with cancer recurrence, metastasis, size or nuclear grade, their differential increase suggests a potential therapeutic target.