Chaves C B P, Nicolau-Neto P, Simão T A, Souza-Santos P T de, Bergmann A, Brewer L, Moreira F C B, Reis B S B, Moreira M A M, Pinto L F R
Seção de Ginecologia Oncológica, Divisão de Pesquisa Clínica e Inovação Tecnológica, Instituto Nacional de Câncer - INCA, Rio de Janeiro, RJ, Brasil.
Programa de Carcinogênese Molecular, Instituto Nacional de Câncer - INCA, Rio de Janeiro, RJ, Brasil.
Braz J Med Biol Res. 2025 May 9;58:e14494. doi: 10.1590/1414-431X2025e14494. eCollection 2025.
Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent subtype. EEC is often associated with favorable clinicopathological features and a good prognosis, especially when diagnosed in stage I. Although some patients have no signs to predict locally advanced or metastatic disease, they may present tumor relapse in the future. There is no biomarker capable of predicting the relapse of stage I EEC. The present study applied a transcriptome analysis to identify differentially expressed genes in stage I EEC, comparing relapsed with non-relapsed tumors. The estrogen receptor 1 gene (ESR1) was overexpressed in EEC stage I samples from patients who developed relapse by 4.3-fold compared to non-relapsed tumors. Subsequently, an independent set of 64 stage I EEC samples was used to validate ESR1 gene overexpression in relapsed tumors and assess estrogen receptor alpha (ERα) protein levels. ESR1 was confirmed to be overexpressed in samples from relapsed tumors, and its expression level was an independent prognostic variable for disease-free (hazard ratio=7.25) and overall survival (hazard ratio=5.15). In contrast, Erα did not show different values between relapsed and non-relapsed tumors. We concluded that ESR1 overexpression is a biomarker for poor prognosis in stage I EEC.
子宫内膜癌（EC）是发达国家最常见的盆腔妇科恶性肿瘤，在发展中国家其发病率也在上升。子宫内膜样子宫内膜癌（EEC）是最常见的亚型。EEC通常与良好的临床病理特征和预后相关，尤其是在I期诊断时。尽管一些患者没有预测局部晚期或转移性疾病的迹象，但他们未来可能会出现肿瘤复发。目前尚无能够预测I期EEC复发的生物标志物。本研究应用转录组分析来鉴定I期EEC中差异表达的基因，将复发肿瘤与未复发肿瘤进行比较。与未复发肿瘤相比，雌激素受体1基因（ESR1）在复发患者的I期EEC样本中过表达4.3倍。随后，使用一组独立的64例I期EEC样本验证复发肿瘤中ESR1基因的过表达，并评估雌激素受体α（ERα）蛋白水平。ESR1在复发肿瘤样本中被证实过表达，其表达水平是无病生存（风险比=7.25）和总生存（风险比=5.15）的独立预后变量。相比之下，ERα在复发肿瘤和未复发肿瘤之间没有显示出不同的值。我们得出结论，ESR1过表达是I期EEC预后不良的生物标志物。
