期刊
CHINESE MEDICAL JOURNAL
卷 132, 期 13, 页码 1550-1562出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CM9.0000000000000286
关键词
Cancer; Endometrial cancer; Heterogeneity
资金
- National Key R&D Program of China [2016YFC1303100, 2016YFC1303103]
- National Natural Science Foundation of China [81502237, 81874108, 81672571, 81802607]
- National Key Technology Research and Development Program of the Ministry of Science and Technology of China [2015BAI13B06]
- Basic Research Project of Peking University [BMU2018JC005]
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 intro-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.
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