异常的DNA甲基化被认为在上皮性卵巢癌(EOC)的化学耐药性中起关键作用。在这项研究中,在高级别浆液性卵巢癌(HGSOC)患者中,我们探讨了桃花素环指1(MGRN1)基因启动子高甲基化与原发性化疗耐药和临床结局之间的关系.MALDI-TOF质谱分析揭示了MGRN1上游区域的高甲基化与HGSOC患者的铂耐药性之间的强关联。Spearman相关分析显示MGRN1甲基化水平与其在HGSOC中的表达呈显著负相关。体外分析证明MGRN1的敲低降低了细胞对顺铂的敏感性,并且EGR1的表达在MGRN1表达水平低的SKOV3细胞中显著降低。同样,铂耐药HGSOC患者EGR1mRNA表达较低,与MGRN1mRNA表达呈正相关。Kaplan-Meier分析显示MGRN1启动子区的高甲基化和MGRN1的低表达与HGSOC患者的较差生存率相关。在多变量模型中,MGRN1低表达是预测预后不良的独立因素。此外,Kaplan-Meier也证实EGR1的低表达与HGSOC患者的不良预后显著相关。MGRN1启动子区的高甲基化和MGRN1的低表达与HGSOC患者的铂类耐药和不良预后有关。可能是通过改变EGR1表达。
Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (
MGRN1) gene promoter and primary chemoresistance and clinical outcomes in high-grade serous ovarian cancer (HGSOC) patients. The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in HGSOC patients. Spearman\'s correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in HGSOC. In vitro analysis demonstrated that knockdown of
MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with MGRN1 mRNA expression. Kaplan-Meier analyses showed that high methylation of the MGRN1 promoter region and low expression of
MGRN1 were associated with worse survival of HGSOC patients. In multivariable models, low
MGRN1 expression was an independent factor predicting poor outcome. Furthermore, low expression of EGR1 was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the
MGRN1 promoter region and low expression of
MGRN1 were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering EGR1 expression.