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.