子宫内膜癌的分子机制及分子分型研究进展

Research Progress on Molecular Mechanism and Molecular Typing of Endometrial Carcinoma

子宫内膜癌近年发病呈上升趋势且发病年龄不断年轻化,晚期子宫内膜癌治疗效果不理想。传统的分类方法在患者的诊疗中存在严重的不足,不能为患者精准治疗提供足够的依据。随着分子生物学的快速发展,越来越多的研究发现子宫内膜癌发病的多组学研究和信号通路关联,临床上迫切需要将其纳入患者的常规诊疗中。传统分型根据有无雌激素刺激将子宫内膜癌分成Ⅰ、Ⅱ两型,Ⅰ型子宫内膜癌的诊断和预后与人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)、磷脂酰肌醇3激酶基因(PI3KCA)、磷酸肌醇3激酶调节亚单位1(PI3KR1)、AT丰富结合域1A(ARID1A)、Kristen鼠肉瘤病毒原癌基因同源体(KRAS)、POLE、CTNNB1、TP53突变,DNA错配修复(MMR)蛋白缺失,雌激素受体(ER)、孕激素受体(PR)表达情况有关。Ⅱ型子宫内膜癌的预后与人表皮生长因子受体2(HER2)过表达、TP53突变、ARID1A突变有关。磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)、P53、丝裂原活化蛋白激酶(MAPK)和Wnt/β-连环蛋白信号通路与子宫内膜癌的发病密切相关。TCGA分型的替代分子分型ProMisE和Parra-Herran分子分型目前被临床用以评估子宫内膜癌的预后与治疗方案,但该分型与预后仍存在部分不匹配的病例,需要对该分型进行进一步细化研究。

The incidence of endometrial carcinoma has been on the rise in recent years and the age of onset is getting younger.The treatment effect of advanced endometrial cancer is not ideal.The traditional classification method has serious deficiencies in the diagnosis and treatment of patients,and cannot provide sufficient basis for accurate treatment of patients.With the rapid development of molecular biology,more and more multi-omics studies and signal pathway associations in the onset of endometrial cancer have been discovered,and there is an urgent clinical need to include it in the routine diagnosis and treatment of patients.This article summarizes the latest progress in molecular biology and signaling pathways of type I and type II endometrial carcinoma.The diagnosis and prognosis of type I endometrial carcinoma are related to PTEN,PI3KCA,PI3KR1,ARID1A,KRAS,POLE,CTNNB1,TP53 mutation,MMR deletion,ER and PR expression are related.The prognosis of type II endometrial cancer is related to HER2 overexpression,TP53 mutation,and ARID1A mutation.PI3K/Akt,P53,MAPK and Wnt/β-catenin signaling pathways are closely related to the pathogenesis of endometrial carcinoma.ProMisE and Parra-Herran molecular classification,an alternative to TCGA classification,are currently used clinically to assess the prognosis and treatment options of endometrial carcinoma,but there are still some cases that do not match the prognosis,further refinement of the typing is needed.