PDF(Pubmed)
Abstract：
Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole, which inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. The increase in Letrozole resistance poses a unique problem for patients. To better understand the underlying molecular mechanism(s) of Letrozole resistance, we reanalyzed transcriptomic data by comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two significant differentially expressed genes (DEGs) between these patient cohorts, with \"PLK1 signaling events\" being the most significant signaling pathway. We also identified PRDX4 and E2F8 gene products as being the top mechanistic transcriptional markers for ER+ treatment resistance. Many of the significant DEGs that we identified play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified are novel in the context of ER+ breast cancer. Many of the genes that we identified warrant further research to elucidate the more specific molecular mechanisms of Letrozole resistance in this patient population and could potentially be used as prognostic markers with further wet lab validation. We anticipate that these findings could contribute to improved detection and therapeutic outcomes in aromatase-resistant ER+ breast cancer patients.
摘要：
雌激素受体阳性（ER+）乳腺癌在绝经后妇女中很常见，经常用来曲唑治疗。抑制芳香酶从雄激素中合成雌激素。雌激素减少减缓肿瘤的生长，可以是一种有效的治疗方法。来曲唑耐药性的增加对患者提出了独特的问题。为了更好地了解来曲唑耐药的潜在分子机制，我们通过比较来曲唑治疗应答者(应答者)和治疗耐药者(无应答者),重新分析了转录组数据.我们确定SOX11和S100A9是这些患者队列之间的两个显著差异表达基因（DEG），“PLK1信号事件”是最重要的信号通路。我们还将PRDX4和E2F8基因产物鉴定为ER+治疗抗性的最高机制转录标记。我们确定的许多重要的DEG在ER+乳腺癌或其他类型的癌症中起着已知的作用，部分验证了我们的结果。我们鉴定的几种基因产物在ER+乳腺癌的背景下是新的。我们鉴定的许多基因值得进一步研究，以阐明该患者群体来曲唑耐药的更具体的分子机制，并可能用作进一步湿实验室验证的预后标志物。我们预计这些发现可能有助于改善芳香化酶抗性ER+乳腺癌患者的检测和治疗结果。
