Clinical Significance And Prognosis Value Of RON Protein Expression In Gastric Carcinoma

【Objective】To investigate the expression of RON protein and its relationship with clinicopathological characteristics of gastric carcinoma and prognosis.【Methods】Gastric carcinoma tissue of 98 patients,29 specimens of paraneoplastic tissue and 10 specimens of normal gastric mucosa were examined using immunohistochemical Envision method.In addition,other gastric carcinoma fresh tissue of 19 patients,corresponding paraneoplastic tissue,8 specimens of normal gastric mucosa were examined using Western-blot method;The expressions of RON in Gastric epithelial cell(GES-1),human gastric cancer cell lines HGC-27,SGC-7901, BGC-803,BGC-823 were detected by Western-blot 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 carcinoma and prognosis.【Results】(1) RON positive rate was 56.1%(55/98) in the gastric carcinoma tissue, and 25.6%(8/29) in the paraneoplastic tissue.There was 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 TNM stage(p=0.001), but 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 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.(4) 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 is significant in gastric carcinoma tissue and corresponding paraneoplastic tissue,but is not expressed in normal gastric mucosa. Expression of RONΔ165 was similarly observed in gastric carcinoma tissue 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 gastric carcinoma,and therefore may represent a useful marker to evaluate the biological activity of gastric carcinoma.