酪氨酸激酶受体RON在胃癌中的表达及意义

目的探讨酪氨酸激酶受体RON在胃癌组织中的表达及与预后的关系。方法采用免疫组化Envision法检测98例胃癌组织、29例癌旁组织和10例正常胃黏膜的RON表达及用Western-blot方法检测19例新鲜胃癌组织、癌旁组织、转移的淋巴结和10例正常胃黏膜中RON的表达情况，检测正常胃黏膜上皮细胞GES-1、胃癌细胞株HGC．27、SGC-7901、BGC．803和BGC。823的RON蛋白表达。对所有胃癌术后患者进行随访，随访期为3—89（中位时间22）个月，生存率的比较用Kaplan—Meier法估计生存曲线。结果（1）98例胃癌组织RON阳性表达率为56．1％（55／98），29例癌旁组织RON阳性表达率为27．6％（8／29），两者比较差异有统计学意义（P=0．007）；正常胃黏膜不表达RON；（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关（P〈0．05或P〈0．01），而与Borrmann分型、组织学类型及是否伴远处转移无关（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=0．195）；（4）胃癌新鲜组织，相应癌旁组织和伴有胃癌转移的淋巴结中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；（5）正常人胎儿胃黏膜上皮细胞GES-1、胃癌细胞株SGC-7901、BGC-803、BGC-823均有不同程度的RON蛋白表达，而未分化胃癌细胞株HGC-27未发现有RON蛋白表达。结论RON主要表达于胃癌组织而不表达于正常胃黏膜，并且与胃癌的浸润深度、是否伴有淋巴结转移和胃癌临床病理分期有关，提示RON在人胃癌发生、发展和浸润转移方面发挥重要作用。

Clinical significance of expression of the RON receptor tyrosine kinase in gastric carcinomas

Objective To investigate the expression of recepteur dOrigine nantais （RON） protein and its relationship with clinicopathological characteristics of gastric carcinoma and prognosis. Methods Gastric carcinoma tissues of 98 patients, 29 specimens of paraneoplastic tissues, and 10 specimens of normal gastric mucosa were examined using immunohistochemical Envision method. In addition, other gastric carcinoma fresh tissues of 19 patients, corresponding paraneoplastic tissues, and 8 specimens of normal gastric mucosa were examined using Western blotting method. The expressions of RON in gastric epithelial cell （ GES-1 ）, and human gastric cancer cell lines HGC-27, SGC-7901, BGC-803, and BGC-823 were detected by Western blotting method. All cases were followed up for 3 - 89 months （ median time ： 22 months）. The statistical formula was used to analyze the relationship between RON and clinicopathological characteristics of gastric carcinomas and prognosis. Results （1）RON positive rate was 56. 1% （55/98） in the gastric carcinoma tissues, and 27.6% （8/29） in the paraneoplastic tissues, with a significant statistical difference （ P = 0. 007）. 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. 019）, perigastric lymph nodes metastasis （ P =0. 019）, and tumor node metastasis （TNM） stage （ P =0. 001 ） ; however, was independent of growing manner of the tumor（Borrmann） （ P = 0. 209）, histopathological grade （ P = 0. 196） of the tumor, and distant metastasis （ P =0. 400）. （3）RON expression was not related to survival rate （ P =0. 195）. （4）The splicing variant of RON was strongly expressed in fresh gastric carcinoma tissues, corresponding paraneoplastic tissues, and perigastric lymph nodes with metastatic carcinoma cells. No expression of the splicing variant of RON was observed in the normal gastric mucosa and normal lymph nodes. （5） Except for HGC-27, the expression of the splicing variant of RON was observed in GES-1 and other human gastric cancer cell lines. Conclusions RON expression was significant in gastric carcinoma tissues and corresponding paraneoplastic tissues, but was not expressed in normal gastric mucosa. Expression of RONA165 was similarly observed in gastric carcinoma tissues and in metastases present in lymph node tissues. We hypothesize that RON and its splice variant play an important role in the occurrence, progression, and metastasis of a gastric carcinoma. Therefore it may represent a useful marker to evaluate the biological activity of gastric carcinomas.