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

Expression of NTs family and its receptor Trk family in ovarian cancer and its correlation with overall survival

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,P<0.001);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(P>0.05)。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(P<0.05)。NGF、NT-3及TrkA表达均与卵巢癌患者的临床病理参数不相关(P>0.05)。NT-5表达与病理分级Ⅱ级的卵巢癌患者的OS相关(P<0.05)。TrkB及TrkC表达与临床分期Ⅲ期的卵巢癌患者的OS密切相关(P<0.05)。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。

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 bette＂ 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 , Ⅱ and Ⅲ,grade Ⅱ ,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 grade Ⅱ （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.