华中科技大学Chaoyang Sun、Gang Chen、Kezhen Li和复旦大学Xiaojun Chen研究组合作，开展了早发性子宫内膜样内膜癌（EEEC）的蛋白质基因组学研究。这一研究成果发表在2024年4月2日出版的国际学术期刊《自然-遗传学》上。

为了阐明EEEC的分子特征，研究人员对215名子宫内膜癌患者进行了大规模多组学研究，其中包括81名EEEC患者。研究揭示了暴露相关突变特征与EEEC之间独特的关联，其特点是特定的CTNNB1和SIGLEC10热点突变以及下游通路的破坏。有趣的是，EEECs中SIGLEC10^Q144K突变导致SIGLEC-10蛋白表达异常，并通过与雌激素受体α相互作用促进孕激素抗性。

研究还发现了在EEEC保胎治疗中孕激素反应的潜在蛋白质生物标志物。总之，该研究建立了EEECs的蛋白质基因组资源，揭示了暴露组和基因组易感性之间的相互作用，有助于开发EEECs的一级预防和早期检测策略。

研究人员表示，子宫内膜癌仍然是一个公共卫生问题，其发病率越来越高，尤其是在年轻女性中。保留生育能力是治疗早发性子宫内膜样内膜癌的一个重要考虑因素，尤其是对40岁以下具有生育欲望和能力的患者而言。

附：英文原文

Title: Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response

Author: Hu, Zhe, Wu, Zimeng, Liu, Wei, Ning, Yan, Liu, Jingbo, Ding, Wencheng, Fan, Junpeng, Cai, Shuyan, Li, Qinlan, Li, Wenting, Yang, Xiaohang, Dou, Yingyu, Wang, Wei, Peng, Wenju, Lu, Funian, Zhuang, Xucui, Qin, Tianyu, Kang, Xiaoyan, Feng, Chenzhao, Xu, Zhiying, Lv, Qiaoying, Wang, Qian, Wang, Chao, Wang, Xinyu, Wang, Zhiqi, Wang, Jianliu, Jiang, Jie, Wang, Beibei, Mills, Gordon B., Ma, Ding, Gao, Qinglei, Li, Kezhen, Chen, Gang, Chen, Xiaojun, Sun, Chaoyang

Issue&Volume: 2024-04-02

Abstract: Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

DOI: 10.1038/s41588-024-01703-z

Source: https://www.nature.com/articles/s41588-024-01703-z