Skip to main content

ORIGINAL RESEARCH article

Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1541562

The Impact of Integrated Genomic Analysis on Molecular Classifications and Prognostic Risk Stratification in Endometrial Cancer

Provisionally accepted
Qian Zheng Qian Zheng 1Di Shao Di Shao 2Jin Shu Jin Shu 1Qin Zhang Qin Zhang 1Min Huang Min Huang 2Dong Wang Dong Wang 1*Dongling Zou Dongling Zou 1*
  • 1 Cancer Hospital, Chongqing University, Chongqing, China
  • 2 BGI Genomics, Shenzhen , China., China

The final, formatted version of the article will be published soon.

    Background:The molecular classification of endometrial cancer (EC), as proposed by The Cancer Genome Atlas (TCGA), has transformed tumor classification, but there is a lack of extensive research on the molecular profiles and subtyping of endometrial cancer patients in China.Methods:200 EC Patients were classified into the following four molecular types: (i) POLEmut; (ii) MSI-H; (iii) TP53mut; (iv) NSMP.This study aimed to investigate the molecular characteristics of EC patients at a single center by large-scale next generation sequencing(NGS), including clinicopathological features and gene mutations in patients with distinct molecular types, and to assess the relevance of molecular subtyping for postoperative adjuvant therapy. Results: NSMP group was the most prevalent, comprising 46.0% (92/200) of cases, followed by the TP53mut group at 17.5% (35/200), the MSI-H group at 23.5% (47/200), and the POLEmut group at 13.0% (26/200). CTNNB1 mutations were common in the POLEmut group but rare in the TP53mut group. With the application of the new European Society for Medical Oncology (ESMO) 2022 classification, 27 patients (14.1%) were reclassified. Concordance between the two classifications regarding postoperative risk was observed in 85.9% (165/192) of cases. Seven patients (3.6%) were downstaged, and twenty patients (10.4%) were upgraded.Additionally, the analysis revealed that eleven genes were significantly mutated in patients with lymphovascular space invasion (LVSI) compared to those without LVSI. Notably, NSD3 and POLD1 were highly mutated in patients with lymphatic metastasis compared to those without lymphatic metastasis.Conclusively, large-scale NGS has revolutionized EC management by facilitating rapid molecular subtype identification, guiding tailored adjuvant therapies, targeted treatments, and immunotherapies, and efficiently screening for Lynch syndrome, thereby significantly improving patient outcomes.

    Keywords: endometrial cancer, Molecular classification, next generation sequencing (NGS), adjuvant therapy, Genetic Tumor Syndromes

    Received: 08 Dec 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Zheng, Shao, Shu, Zhang, Huang, Wang and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dong Wang, Cancer Hospital, Chongqing University, Chongqing, China
    Dongling Zou, Cancer Hospital, Chongqing University, Chongqing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.