PKM2在子宫内膜浆液性癌中的表达及其与病情进展的相关性

The Expression of PKM2 in Endometrial Serous Carcinoma and Its Correlation with Disease Progression

目的分析丙酮酸激酶M2(PKM2)在子宫内膜浆液性癌(ESC)中的表达与临床特征及预后的相关性,为揭示ESC早期诊断和治疗的新靶标提供依据。方法从2016年1月至2017年5月,从我院妇瘤科手术病理档案中检索出135例子宫内膜病变患者,包括13例子宫内膜萎缩作为良性病变组,17例子宫内膜息肉样增生伴不典型异型增生作为癌前病变组,30例浆液性子宫内膜上皮内癌(SEIC)作为原位癌组,32例浆液性和子宫内膜样混合型癌(MSE)和43例(21.9%)浆液性癌都作为ESC组。采用免疫组织化学染色法检测PKM2表达,分析PKM2表达与ESC患者不同临床特征的关系。绘制Kaplan-Meier生存曲线,并使用Logistic回归模型和Log-rank分析PKM2表达与预后的相关性。结果基于TCGA数据库分析,子宫内膜癌组织中PKM2 mRNA表达明显高于癌旁正常组织(P<0.001),FIGO分期越高,组织PKM2 mRNA表达越高(P<0.05);且高表达PKM2预示着肿瘤分化差和预后不良(P<0.001)。此外SEA和MSE组织中PKM2 mRNA表达量明显高于EEA组织(P<0.001)。在临床样本中,ESC组织中PKM2蛋白阳性表达率显著高于良性病变组、癌前病变组、原位癌组[0(0/13)vs 17.65%(3/17)vs 30.0%(9/30)vs 64.0%(48/75),χ^(2)=29.498,P<0.001]。且ESC组织PKM2表达与子宫肌层浸润、淋巴管浸润、FIGO分期有关(P<0.05)。经Kaplan-Meier生存曲线和Log Rankχ^(2)检验,PKM2蛋白高表达组患者5年生存率低于低表达组[60.4%(29/48)vs 74.1%(20/27),χ^(2)=3.481,P=0.015];且组织PKM2蛋白高表达是影响患者预后的独立危险因素(P<0.05)。结论PKM2蛋白表达水平可作为ESC和癌前病变、SEIC鉴别诊断的生物标志物。此外,对于ESC患者,组织PKM2蛋白高表达似乎也预示着患者5年生存预后不良。

Objective To analyze the correlation between the expression of pyruvate kinase M2(PKM2)in endometrial serous carcinoma(ESC)and its clinical characteristics and prognosis,and to provide a knowledge basis for revealing a new target for the early diagnosis and treatment of ESC.Methods From January,2016 to May,2017,a total of 135 cases of endometrial diseases were retrieved from the surgical and pathological files of Gynecologic Oncology Department,including 13 cases of intrauterine membrane atrophy as the benign lesion group,17 cases of intrauterine membrane polypoid hyperplasia with atypical hyperplasia as the precancerosis group,30 cases of serous temper intrauterine membrane intraepithelial carcinoma group(SEIC)as the carcinoma in situ group,and 32 cases of mixed serous and endometrioid carcinoma(MSE)and 43 cases of serous carcinoma(21.9%)were included in the ESC group.Immunohistochemical staining was conducted to detect PKM2 expression level,and the relationship between PKM2 expression and different clinical characteristics of ESC patients was analyzed.Kaplan-Meier survival curve was plotted,and logistic regression model and Log-rank test were used to analyze the correlation between PKM2 expression and prognosis.Results Based on TCGA database analysis,the expression of PKM2 mRNA in endometrial cancer tissues was significantly higher than that in adjacent normal tissues(P<0.001),and the higher FIGO stage,the higher PKM2 mRNA expression in tissues(P<0.05).High PKM2 expression was able to predict poor tumor differentiation and poor prognosis(P<0.001).In addition,the expressions of PKM2 mRNA in SEA and MSE tissue were significantly higher than that in EEA tissue(P<0.001).In clinical samples,the positive expression rate of PKM2 protein in ESC tissue was significantly higher than that in the lesion group,precancerosis group and carcinoma in situ group[0(0/13)vs 17.65%(3/17)vs 30.0%(9/30)vs 64.0%(48/75),χ^(2)=29.498,P<0.001].PKM2 expression in ESC was correlated with myometry invasion,lymphatic invasion and FIGO stage(P<0.05).Kaplan-Meier survival curve and Log Rankχ^(2) test showed that the 5-year survival rate of patients with high PKM2 protein expression was lower than that of patients with low PKM2 protein expression[60.4%(29/48)vs 74.1%(20/27),χ^(2)=3.481,P=0.015].In addition,the high expression of PKM2 protein in tissues was an independent risk factor for the prognosis of patients(P<0.05).Conclusion PKM2 is closely related to the occurrence and development of ESC,and its expression level is negatively correlated with the prognosis of ESC patients,which can be used as a molecular biological indicator for the early diagnosis or potential therapeutic targets of ESC.