内源性硫化氢及其合成酶在膀胱癌恶性进展中的表达

Expression of endogenous hydrogen sulfide and its synthases in urothelial cell carcinoma of bladder

目的探讨内源性硫化氢(H2S)及其合成酶胱硫醚-β-合成酶(CBS)、胱硫醚-γ-裂解酶(CSE)和3-巯基丙酮酸硫转移酶(MPST)在正常膀胱组织以及膀胱癌中的表达。方法选取因膀胱癌而行膀胱肿瘤电切术或膀胱癌根治术的肿瘤组织标本76例,同时收集15例正常膀胱组织作对照组。通过免疫组化和Western blot研究CBS、CSE和MPST在正常膀胱组织以及不同病理分期/分级膀胱癌组织中的表达情况;通过敏感硫电极法检测H2S在正常膀胱组织和膀胱癌中的含量。分别比较H2S及其合成酶在各组之间的差异,初步探讨H2S及其合成酶与膀胱癌恶性进展之间的关系。结果免疫组化结果显示CBS(79.1%)、CSE(81.3%)和MPST(84.6%)在膀胱癌黏膜和肌层组织中均有表达。CBS(P=0.021和P<0.001)和MPST(P=0.015和P=0.045)的表达在膀胱癌不同分期和分级之间有统计学差异。在所有检测的标本中,肌层浸润性膀胱癌中的H2S含量最高[(52.6±2.91)nmol·mg-1·min-1],各组之间有统计学差异。结论内源性H2S及其合成酶CBS、CSE和MPST在膀胱癌组织中的表达明显高于正常膀胱组织,且其表达在膀胱癌不同分期和分级之间有统计学差异。

Objective To evaluate endogenous hydrogen sulfide （H2S） production and its synthases cystathionineβ-synthase （CBS）, cystathionineγ-lyase （CSE） and 3-mercaptopyruvate sulfurtransferase （MPST） expression levels in urothelial cell carcinoma of bladder （UCB） tissue. Methods 76 samples of UCB tissues and 15 samples of normal tissues were obtained from patients who had undergone either transurethral resection or radical cystectomy for bladder cancer. The expression levels/activities of CBS, CSE, and MPST of specimens were analyzed by image semi-quantity assay, Western blot and a sulfur-sensitive electrode. The relativity of the expression of H2S and its synthases in bladder tissues and its correlation with the UCB were further studied. Results Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined. The expression levels of CBS and MPST were associated with UCB stage/grade. MIBC samples showed highest production of H2S among all tested samples. Conclusion UCB tissue had increased protein levels and catalytic activities of CBS, CSE, and MPST compared to benign tissue which associated with stage/grade.