Hepsin在胃癌中表达下调并提示预后不良

Hepsin is Down-regulated in Gastric Cancer and Predicts a Poor Prognosis

背景:Ⅱ型跨膜丝氨酸蛋白酶hepsin在前列腺癌、卵巢癌、乳腺癌等多种原发肿瘤中呈高表达,并与肿瘤进展和预后不良相关。目的:探讨hepsin在胃癌中的表达模式及其与胃癌临床病理特征和预后的关系。方法:纳入40对原发性胃癌组织和相应正常胃黏膜,以cDNA微阵列技术筛选两者间的差异表达基因,并以real-time PCR进行验证。以免疫组化方法检测其中20例胃癌组织以及另100例胃癌组织石蜡切片中的hepsin蛋白表达,分析其表达与胃癌临床病理特征和预后的关系。结果:cDNA微阵列分析显示胃癌组织中的hepsin基因表达较正常胃黏膜显著下调(ratio=0.240),real-time PCR结果与cDNA微阵列分析一致(P=0.002)。83例(69.2%)胃癌组织hepsin蛋白表达阴性,其余为弱阳性表达。Kaplan-Meier曲线显示hepsin蛋白表达阴性者总体生存率显著低于hepsin蛋白表达弱阳性者(P<0.0001)。单因素分析显示hepsin蛋白表达与胃癌浸润深度(P=0.043)和患者总体生存率(P=0.018)相关,多因素Cox回归分析显示hepsin蛋白表达为胃癌预后的保护因素(RR=0.599,P=0.000)。结论:Hepsin在胃癌组织中表达下调,并与胃癌进展和预后不良相关。

Background： Hepsin is a type II transmembrane serine protease found to be highly expressed in various primapy tumors （e. g. prostate, ovarian and breast cancer） and is correlated with tumor progression and poor prognosis. Aims： To investigate the expression profile of hepsin in gastric cancer and its correlation with clinicopathological characteristics and prognosis. Methods： Differentially expressed genes were screened by cDNA microarray and confirmed by real-time PCR in matched gastric tissue samples from cancerous and noncancerous parts of 40 primary gastric cancers. Expression of hepsin protein in 20 above-mentioned gastric cancer tissues and 100 paraffin-embedded gastric cancer tissues was assessed by immunohistochemistry. Relationship between hepsin protein expression and clinicopathological characteristics and prognosis of gastric cancer was analyzed. Results： cDNA microarray revealed that hepsin gene was down-regulated in gastric cancer tissues （ ratio = 0. 240）, and real-time PCR confirmed that there was a significant difference in hepsin mRNA expression between gastric cancer tissues and normal gastric mucosa （ P = 0. 002）. Eighty-three （69.2%） gastric cancer tissues were negative for hepsin protein expression, while the other 37 tissues presented weakly positive immunostaining. Kaplan-Meier curve demonstrated that negative hepsin protein expression was associated with reduced overall survival （ P 〈 0. 0001 ）. Univariate analysis showed that hepsin protein expression in gastric cancer was correlated with depth of tumor invasion （ P = 0.043） and overall survival （P = 0. 018）, while multivariate analysis by Cox regression showed that hepsin protein expression favored the prognosis of gastric cancer （ RR = 0. 599, P = 0. 000）. Conclusions ： Hepsin is down-regulated in gastric cancer and significantly correlated with tumor progression and poor prognosis.