Intra-tumor heterogeneity for endometrial cancer and its clinical significance  

作　　者：Fu-Fen Yin Li-Jun Zhao Xiao-Yu Ji Ning Duan Yan-Kui Wang Jing-Yi Zhou Li-Hui Wei Xiang-Jun He Jian-Liu Wang Xiao-Ping Li 

机构地区：[1]Department of Obstetrics and Gynecology,Peking University People's Hospital,Beijing 100044,China [2]Department of Obstetrics and Gynecology,Affiliated Hospital of Qingdao University,Qingdao,Shandong 266000,China

出　　处：《Chinese Medical Journal》2019年第13期1550-1562,共13页中华医学杂志（英文版）

基　　金：grants from the National Key R&D Program of China(Nos.2016YFC1303100,2016YFC1303103);the National Natural Science Foundation of China(Nos.81502237,81874108,81672571,and 81802607);National Key Technology Research and Development Program of the Ministry of Science and Technology of China(No.2015BAI13B06);Basic Research Project of Peking University(No.BMU2018JC005).

摘　　要：Background:Management of tumors has become more complex owing to tumor heterogeneity.Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer(EC)until now.Therefore,it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.Methods:A total of 1688 patients with EC were screened and 114 patients were finally selected,including specimens from 84 patients with primary EC without relapse(PE)and the paired metastases(P-M)specimens,as well as specimens from 30 patients with primary EC with relapse(RPE)and the paired relapsed EC(P-RE)specimens.Microarray and RNA-seq were used to detect gene expression of EC samples.Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.Results:The clinical intra-tumor spatial heterogeneity of pathological type,grade,ER status,and PR status between PE and P-M were 17.9%,13.1%,28.6%,and 28.6%,respectively.The clinical intra-tumor spatiotemporal heterogeneity of pathological type,grade,ER status,and PR status between RPE and P-RE were 16.7%,33.3%,25.0%,and 37.5%,respectively.Cluster analysis sorts EC samples based on progression type of lesion and their pathological type.There were differentially expressed genes between PE and P-M and between RPE and P-RE,of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation,the p53 signaling pathway,etc.Conclusions:Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC,which may add to the complexity of diagnosis and therapeutics for EC.Considering the intra-tumor heterogeneity,sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

关 键 词：CANCER ENDOMETRIAL CANCER HETEROGENEITY 

分 类 号：R[医药卫生]