Prognostic significance and clinical relevance of Sprouty 2 protein expression in human hepatocellular carcinoma  

作　　者：Kang Song,Qiang Gao,Jian Zhou,Shuang-Jian Qiu,Xiao-Wu Huang,Xiao-Ying Wang and Jia Fan Liver Cancer Institute, Zhongshan Hospitaland Institute of Biomedical Sciences , Fudan University, Shanghai 200032, China 

出　　处：《Hepatobiliary & Pancreatic Diseases International》2012年第2期177-184,共8页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Key Sci-Tech Special Project of China(2008ZX10002-018/019);the Shanghai Rising-Star Program(10QA1401300);the National Natural Science Foundation of China(30901432);the Research Fund for the Doctoral Program of Higher Education of China (20090071120026)

摘　　要：BACKGROUND:In vitro experiments and mice models have confirmed the importance of Sprouty 2(Spry2) in inhibiting tumorigenesis and the progression of human cancer.However,the prognostic value of Spry2 in cancer patients remains unknown.This study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma(HCC).METHODS:With samples from 240 randomly-selected HCC patients who underwent surgery,immunohistochemistry was used to investigate Spry2 expression on tissue microarrays.The correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression analysis.Spry2,ERK and phospho-ERK expression in HCC cell lines was detected by Western blotting.RESULTS:Among the patients,86.3%(207 of 240) exhibited down-regulation of Spry2 expression.Patients negative for Spry2 showed poorer survival(P=0.002) and increased recurrence(P=0.003).Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients(HR=1.47;95% CI,1.02-2.08;P=0.037).Downregulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages,and was positively correlated with the metastatic potential of HCC cell lines.CONCLUSION:In the era of molecular targeted therapy,the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.BACKGROUND:In vitro experiments and mice models have confirmed the importance of Sprouty 2(Spry2) in inhibiting tumorigenesis and the progression of human cancer.However,the prognostic value of Spry2 in cancer patients remains unknown.This study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma(HCC).METHODS:With samples from 240 randomly-selected HCC patients who underwent surgery,immunohistochemistry was used to investigate Spry2 expression on tissue microarrays.The correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression analysis.Spry2,ERK and phospho-ERK expression in HCC cell lines was detected by Western blotting.RESULTS:Among the patients,86.3%(207 of 240) exhibited down-regulation of Spry2 expression.Patients negative for Spry2 showed poorer survival(P=0.002) and increased recurrence(P=0.003).Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients(HR=1.47;95% CI,1.02-2.08;P=0.037).Downregulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages,and was positively correlated with the metastatic potential of HCC cell lines.CONCLUSION:In the era of molecular targeted therapy,the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.

关 键 词：hepatocellular carcinoma Sprouty 2 tumor suppressor PROGNOSIS 

分 类 号：R735.7[医药卫生—肿瘤]