Li Yimin, Tian Ruotong, Liu Jiaxin, Ou Chunlin, Wu Qihui, Fu Xiaodan
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Mol Biosci. 2022 Apr 26;9:833910. doi: 10.3389/fmolb.2022.833910. eCollection 2022.
Accumulating evidence suggests that anti-estrogens have been effective against multiple gynecological diseases, especially advanced uterine corpus endometrial carcinoma (UCEC), highlighting the contribution of the estrogen response pathway in UCEC progression. This study aims to identify a reliable prognostic signature for potentially aiding in the comprehensive management of UCEC. Firstly, univariate Cox and LASSO regression were performed to identify a satisfying UCEC prognostic model quantifying patients' risk, constructed from estrogen-response-related genes and verified to be effective by Kaplan-Meier curves, ROC curves, univariate and multivariate Cox regression. Additionally, a nomogram was constructed integrating the prognostic model and other clinicopathological parameters. Next, UCEC patients from the TCGA dataset were divided into low- and high-risk groups according to the median risk score. To elucidate differences in biological characteristics between the two risk groups, pathway enrichment, immune landscape, genomic alterations, and therapeutic responses were evaluated to satisfy this objective. As for treatment, effective responses to anti-PD-1 therapy in the low-risk patients and sensitivity to six chemotherapy drugs in the high-risk patients were demonstrated. The low-risk group with a relatively favorable prognosis was marked by increased immune cell infiltration, higher expression levels of HLA members and immune checkpoint biomarkers, higher tumor mutation burden, and lower copy number alterations. This UCEC prognostic signature, composed of 13 estrogen-response-related genes, has been identified and verified as effective. Our study provides molecular signatures for further functional and therapeutic investigations of estrogen-response-related genes in UCEC and represents a potential systemic approach to characterize key factors in UCEC pathogenesis and therapeutic responses.
越来越多的证据表明，抗雌激素药物对多种妇科疾病有效，尤其是晚期子宫体子宫内膜癌（UCEC），这突出了雌激素反应途径在UCEC进展中的作用。本研究旨在确定一个可靠的预后特征，以辅助UCEC的综合管理。首先，进行单变量Cox和LASSO回归，以确定一个令人满意的UCEC预后模型，该模型根据雌激素反应相关基因量化患者风险，并通过Kaplan-Meier曲线、ROC曲线、单变量和多变量Cox回归验证其有效性。此外，构建了一个整合预后模型和其他临床病理参数的列线图。接下来，根据TCGA数据集中UCEC患者的中位风险评分将其分为低风险组和高风险组。为了阐明两个风险组之间生物学特征的差异，评估了通路富集、免疫景观、基因组改变和治疗反应以实现这一目标。在治疗方面，低风险患者对抗PD-1治疗有有效反应，高风险患者对六种化疗药物敏感。预后相对较好的低风险组的特征是免疫细胞浸润增加、HLA成员和免疫检查点生物标志物的表达水平较高、肿瘤突变负担较高以及拷贝数改变较低。这个由13个雌激素反应相关基因组成的UCEC预后特征已被确定并验证是有效的。我们的研究为UCEC中雌激素反应相关基因的进一步功能和治疗研究提供了分子特征，并代表了一种潜在的系统方法来表征UCEC发病机制和治疗反应中的关键因素。
