自噬相关基因Beclin1和LC3在卵巢浆液性癌中的表达及临床意义

Expression of autophagy-related genes Beclin1 and LC3 in ovarian serous carcinoma and their clinical significance

目的检测Beclin1和LC3在卵巢浆液性癌(ovarian serous carcinoma,OSC)中的表达,探讨两者与OSC临床病理特征及预后的关系。方法采用免疫组化Max Vision两步法检测63例OSC和20卵巢浆液性囊腺瘤组织中Beclin1和LC3蛋白的表达,分析两者与OSC临床病理特征及预后的关系。应用RT-PCR和Western blot法检测10例新鲜OSC组织和相应癌旁组织中Beclin1和LC3 mRNA和蛋白的表达。结果在OSC组织中Beclin1和LC3蛋白阳性率(36.51%、33.33%)均低于卵巢浆液性囊腺瘤组织(65.00%、60.00%),差异有统计学意义(P=0.025,P=0.034)。Beclin1蛋白表达与临床FIGO分期和病理分级有关(P=0.001,P=0.001),与患者年龄、发病部位、肿瘤大小及有无盆腔淋巴结转移无关(P>0.05)。LC3蛋白表达与临床FIGO分期和盆腔淋巴结转移有关(P=0.013,P=0.041),与患者年龄、发病部位、肿瘤大小和病理分级均无关(P>0.05)。Beclin1和LC3在OSC中的表达呈显著正相关(r_s=0.373,P=0.03)。10例新鲜OSC组织中Beclin1和LC3 mRNA的相对表达量(0.581±0.091、0.650±0.090)低于癌旁组织,两者比较差异有统计学意义(t=8.083,t=6.614;P=0.016,P=0.022)。新鲜OSC组织中Beclin1和LC3蛋白的相对表达量明显低于癌旁组织,两者比较差异有统计学意义(P<0.05)。Kaplan-Meier生存分析表明,Beclin1和LC3表达与OSC患者预后相关(P=0.028 3,P=0.018 5)。结论自噬相关基因Beclin1和LC3在OSC组织中的表达下降,导致自噬功能减弱,可能与OSC的发生、发展和预后不良相关。

Purpose To detect the expression of autoph- agy-related genes Beclinl and microtubule-associated proteinl light chain3 （LC3） in ovarian serous carcinoma （OSC） and to analyze the correlations with clinical pathological characteristics and prognosis of patients with OSC. Methods Immunohisto- chemical staining of MaxVision two-step was performed to detect the expression of Beclinl and LC3 in the samples from 63 OSC patients and 20 with benign ovarian serous cystadenomas. The relation between Beclinl and LC3 with the factors influencing the prognosis of OSC was investgated. The expression levels of mR- NA and proteins in 10 fresh OSC samples and their correspond- ing adjacent noncancerous tissues were examined by RT-PCR and Western blot. Results The positive percentage of Bec- linl and LC3 protein in the tissues of OSC was 36. 51% and 33.33%, which was significantly lower than that of 65.00% and 60.00% in serous cystadenomas （P =0. 025, P =0. 034）. The expression of Beclinl in OSC was significantly correlated with clinical FIGO stage and pathological grade （ P = 0. 001, P =0. 001 ）, but not associated with age, site, tumor size and lymph node metastasis （P 〉 0. 05）. The expression of LC3 protein in OSC was significantly with clinical FIGO stage and lymph node metastasis （ P = 0. 013, P = 0. 041 ）, but not associated with age, site, tumor size and pathological grade （ P 〉 0.05 ）. There was a positive correlation between Beclinl and LC3 in OSC （r^2 = 0. 373, P = 0. 03）. The levels of Becliul and LC3 mRNA （0. 581 ±0. 091, 0. 650 ±0. 090） in 10 fresh OSC were significantly lower than in their adjacent noncancerous tissues （t = 8.083, t = 6. 614, P = 0. 016, P = 0. 022）. The levels of Be- clinl and LC3 protein in 10 fresh OSCs were significantly lower than in their adjacent tissues （ P 〈 0. 05 ）. Kap- 1an-Meier survival analyses revealed that the expression of Beclinl and LC3 were associated with the patients prognosis （ P = O. 028 3, P = 0. 018 5）. Conclusion Expression of Beclinl and LC3 protein is down-regulated in the tissues of OSC which lead to decrease of function of autophagy. The decrease of Beclinl and LC3 may be associated with the development and prog- nosis of OSC.