Intra-tumor heterogeneity for endometrial cancer and its clinical significance
10.1097/CM9.0000000000000286
- Author:
Fu-Fen YIN
1
;
Li-Jun ZHAO
1
;
Xiao-Yu JI
2
;
Ning DUAN
2
;
Yan-Kui WANG
2
;
Jing-Yi ZHOU
1
;
Li-Hui WEI
1
;
Xiang-Jun HE
1
;
Jian-Liu WANG
1
;
Xiao-Ping LI
1
Author Information
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
- Publication Type:Journal Article
- Keywords:
Cancer;
Endometrial cancer;
Heterogeneity
- From:
Chinese Medical Journal
2019;132(13):1550-1562
- CountryChina
- Language:English
-
Abstract:
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.
