Hedgehog信号通路在肾透明细胞癌中的表达及作用

Expression and Role of Hedgehog Signaling Pathway in Renal Clear Cell Carcinoma

目的研究人肾透明细胞癌(RCCC)中Hedgehog信号通路相关因子Shh、Ptch、Smo和Gli1蛋白的表达,探讨Hedgehog信号转导通路的异常激活与RCCC的关系。方法应用免疫组织化学方法检测76例RCCC标本及12例癌旁正常肾组织,应用蛋白免疫印迹技术检测10例新鲜癌组织及癌旁正常肾组织中Shh、Ptch、Smo和Gli1蛋白的表达。结果 Shh、Ptch、Smo和Gli1蛋白在RCCC中的异常表达率(分别为52.6%、63.2%、44.7%、60.5%)高于正常肾组织(分别为8.3%、16.7%、8.3%、25.0%)。且其表达与患者的年龄、性别和肿瘤大小无显著相关,而与肿瘤临床分期有关,随肿瘤的恶性程度加重,表达率增加。结论 Hedgehog信号转导通路在RCCC中呈现高度激活状态,此通路的激活可能与RCCC的发生、发展密切相关,有望成为治疗RCCC的靶点。

Objective To investigate the expression of Shh, Ptch, Smo and Gli1 proteins who belongs to componentsof Hedgehog signaling pathway, and to explore the relationship between the abnormal activated of Hedgehog signaling path-way with renal clear cell carcinoma（RCCC）. Methods Protein expressions were examined by immunohistochemistry in 76 cases of human RCCC and 12 pericarcinomatous tissues. And 10 fresh specimens from cancer tissues and pericarcinoma-tous tissues were used to examine expressions of Shh, Ptch, Smo and Gli1 by Western blotting. Results The expressions ofexamined proteins were higher in RCCC than that in pericarcinomatous tissue. Shh（52.6% vs 8.3%）, Ptch（63.2% vs 16.7%）,Smo（44.7% vs 8.3%） and Gli1（60.5% vs 25.0%）. The increased proteins levels were disassociated with age, gender, and tu-morous size in RCCC. But it was significantly correlated with TNM stage of RCCC. The expressions were gradually increasedwith higher TNM stage of RCCC or more invasive malignancy. Conclusion Hedgehog signaling pathway is highly activatedin RCCC. It might be involved in initiation, progression of RCCC, and it might be used as the target for RCCC treatment.