NTs家族成员及其受体Trk在卵巢癌中的表达及其与生存期的相关性

目的:分析神经营养素(NTs)家族成员及其酪氨酸激酶受体(Trk)在卵巢癌中的表达情况及其与患者总生存期(OS)的关系,评价其预后价值。方法:利用KaplanMeier plotter(KM plotter)在线数据库收集卵巢癌患者病理信息,分析NTs家族成员(NGF、BDNF、NT-3、NT-5)及其受体Trk(TrkA、TrkB、TrkC)表达与卵巢癌患者预后及临床病理参数的相关性。收集新鲜卵巢癌组织和癌旁组织各6例,Western blot法检测NTs及Trk蛋白表达。结果:BDNF mRNA高表达与卵巢癌患者较好的总生存期(OS)相关(危险比HR=0.78,95%CI为0.68~0.89,P0.001);NGF、NT-3、NT-5及受体TrkA、TrkB、TrkC表达与卵巢癌患者的总生存期(OS)无关(P0.05)。BDNF mRNA表达与临床分期Ⅰ、Ⅱ及Ⅲ期、病理分级Ⅱ级、组织学分型浆液性癌及TP53野生型的卵巢癌患者的OS密切相关(P0.05)。NGF、NT-3及TrkA表达均与卵巢癌患者的临床病理参数不相关(P0.05)。NT-5表达与病理分级Ⅱ级的卵巢癌患者的OS相关(P0.05)。TrkB及TrkC表达与临床分期Ⅲ期的卵巢癌患者的OS密切相关(P0.05)。Western blot法检测显示,NTs家族中NGF、BDNF、NT-5蛋白在卵巢癌组织中过表达,NT-3蛋白则为低表达;Trk家族中TrkA、TrkB及TrkC在卵巢癌组织中高表达。结论:BDNF表达与卵巢癌患者的预后密切相关,高表达患者的预后更好,可作为潜在的预后指标进行研究;NTs家族其他成员及受体Trk家族均无此预测作用。

Expression of NTs family and its receptor Trk family in ovarian cancer and its correla-tion with overall survival

Objective:To investigate the expressions of Neurotrophins ( NTs) and tyro-sine kinase receptor ( Trk) in ovarian cancer and its correlation with overall survival ( OS) ,and to evaluate its prognosis value. Methods:Kaplan-Meier plotter ( KM plotter) online database was used to collect patients with ovarian cancer,and to analyze the correlation among the ex-pressions of NTs (NGF,BDNF,NT-3,NT-5) and its receptors Trk (TrkA,TrkB,TrkC) and the prognosis and clinical pathological parameters of patients. 6 cases of fresh ovarian cancer tissues and adjacent tissues were collected and NTs and Trk proteins expression were detected by West-ern blot. Results:The mRNA high expression level of BDNF was associated with better overall survival (OS) for ovarian cancer patients (P<0. 001),hazard ratio (HR) was 0. 78,95%CI was 0. 68 ~0. 89. The expressions of NGF, NT-3, NT-5 and receptors TrkA, TrkB and TrkC were not correlated with the overall survival of patients with ovarian cancer ( P>0 . 05 ) . The ex-pression of BDNF mRNA was closely related to the OS for patients with clinical stage Ⅰ,Ⅱand Ⅲ,gradeⅡ,serous and TP53 wild type (P<0. 05). The expressions of NGF,NT-3 and Tr-kA were not correlated with the clinicopathological parameters of ovarian cancer ( P>0 . 05 ) . However,the expression of NT-5 was correlated to the OS for patients with gradeⅡ(P<0. 05), and the expressions of TrkB and TrkC were closely related to the OS for patients with stage III (P<0. 05). Western blot results showed that NGF,BDNF and NT-5 were over-expressed in o-varian cancer tissues, and NT-3 was down-regulated. TrkA, TrkB and TrkC were all over-ex-pressed in ovarian cancer tissues. Conclusion:The expression of BDNF is closely related to the prognosis of ovarian cancer patients,and high expression of BDNF has better prognosis. BDNF will be used as a potential prognostic indicator for cancer. But other members of NTs family and its receptors Trk family have no such predictive effect.