Quintas-Granados Laura Itzel, Cortés Hernán, Carmen Manuel González-Del, Leyva-Gómez Gerardo, Bustamante-Montes Lilia Patricia, Rodríguez-Morales Miguel, Villegas-Vazquez Edgar Yebran, López-Reyes Israel, Alcaraz-Estrada Sofía Lizeth, Sandoval-Basilio Jorge, Soto-Reyes Ernesto, Sharifi-Rad Javad, Figueroa-González Gabriela, Reyes-Hernández Octavio Daniel
Universidad Mexiquense del Bicentenario, Unidad de Estudios Superiores Tultitlán, Mexico, Mexico.
Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, 14389, Mexico City, Mexico.
Cancer Cell Int. 2021 Dec 4;21(1):649. doi: 10.1186/s12935-021-02343-7.
The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers.
Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status.
We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes.
Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker.
ESR1基因在多种癌症中会发生甲基化变化，包括乳腺癌（BC），乳腺癌是女性中最常被诊断出的癌症，男性中也有。就总生存期而言，ESR1启动子A处的甲基化预后较差；因此，早期检测、预后评估和治疗预测涉及一些甲基化生物标志物。
因此，我们的研究旨在检测墨西哥乳腺癌患者样本中ESR1基因的甲基化水平及其与绝经状态的可能关联。
我们在ESR1基因启动子A中鉴定出一个新的151 bp的CpG岛。有趣的是，雌激素受体α（ERα）阳性肿瘤中该CpG岛的甲基化水平比ERα阴性或对照样本低约50%。此外，ESR1的甲基化水平与绝经状态相关。在绝经后患者中，甲基化水平比绝经前患者高1.5倍。最后，根据肿瘤恶性程度，三阴性癌症亚型的ESR1甲基化水平高于管腔型/人表皮生长因子受体2阳性（HER2+）或管腔A型亚型。
我们的研究结果表明，这个新的CpG岛处的甲基化可能是一个有前景的预后标志物。
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