酪氨酸激酶受体RON蛋白质在胃癌患者中的表达及其临床意义

目的 探讨RON蛋白在人胃癌组织中表达及与预后关系.方法 采用免疫组织化学技术检测胃癌、癌旁和正常胃黏膜组织的RON表达及用免疫印迹技术检测新鲜胃癌、癌旁、伴转移的淋巴结和正常对照组织的RON表达,并对胃癌术后患者进行随访(3～89个月).结果 (1)胃癌组织RON表达率为56.1%(55/98),癌旁组织为25.6%(8/29)(P＜0.01),而正常胃黏膜不表达;(2)RON表达与胃癌细胞浸润深度、有否伴淋巴结转移和临床病理分期有明显关系(均P＜0.05),而与Borrmann分型、组织学类型及是否伴远处转移无明显关系(均P＞0.05);(3)RON阳性表达组与阴性组术后生存率差异无统计学意义(P＞0.05);(4)新鲜胃癌组织,相应癌旁组织和伴转移的淋巴结中RON变异体(RONA165)均呈强表达,而正常胃黏膜和正常淋巴结未见RON变异体表达.结论 RON在胃癌发生,发展和转移过程中扮演重要作用,其对评估胃癌生物学行为有一定参考价值.

Clinical significance and prognostic value of RON protein expression in gastric carcinoma

Objective To investigate the protein expression of RON, a tyrosine kinase receptor,protein in gastric carcinoma and the relationship between its expression and prognosis of cancer. Methods 98 samples of gastric carcinoma obtained from 98 patients, 70 males and 28 females, aged 58 (21-76), 29 specimens of paraneoplastic tissue, and 10 specimens of normal gastric mucosa were examined using immunohistochemical Envision method; 19 samples of gastric carcinoma fresh tissue, paraneoplastic tissue,and paraneoplastic lymph nodes with metastasis obtained from patients during operation underwent Western blotting to detect the protein expression of RON. And 10 specimens of normal gastric mucosa and normal lymph nodes were examined as controls. All cases were followed up for 3-89 months. Results (1) The RON positive rate of the gastric carcinoma tissue was 56.1% (55/98), significantly higher than that of the paraneoplastic tissue (25.6%, 8/29, P＜0.01 ). No RON expression was observed in the normal gastric mucosa. (2)RON expression was positively correlated with the invasive depth of the tumor (P＜0.05 ),perigastric lymph nodes metastasis ( P＜0.05 ), and TNM stage ( P＜0.01 ), but was not correlated with the growing manner of the tumor (Borrmann staging), histopathological grade of the tumor, and distant metastasis ( all P＞0.05 ). (3) RON expression was not related to the survival rate ( P＞0.05 ). (4) The splicing variant of RON was strongly expressed in the fresh gastric carcinoma tissue, corresponding paraneoplastic tissue and perigastric lymph nodes with metastatic carcinoma cell. No expression of the splicing variant of RON was observed in the normal gastric mucosa and normal lymph nodes. Conclusion RON and its splice variant may play an important role in the pathogenesis, progression, and metastasis of gastric carcinoma, and represent potential markers that can be used to evaluate the biological activity of gastric carcinoma.