AUTHOR=Li Xiao-fei , Sun Hai-yan , Hua Tian , Zhang Hai-bo , Tian Yun-jie , Li Yan , Kang Shan 

TITLE=Promoter Methylation of the MGRN1 Gene Predicts Prognosis and Response to Chemotherapy of High-Grade Serous Ovarian Cancer Patients

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.659254

DOI=10.3389/fonc.2021.659254

ISSN=2234-943X

ABSTRACT=<p>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 (<italic>MGRN1</italic>) 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 <italic>MGRN1</italic> upstream region and platinum resistance in HGSOC patients. Spearman’s correlation analysis revealed a significantly negative connection between the methylation level of <italic>MGRN1</italic> and its expression in HGSOC. In vitro analysis demonstrated that knockdown of <italic>MGRN1</italic> reduced the sensitivity of cells to cisplatin and that expression of <italic>EGR1</italic> was significantly decreased in SKOV3 cells with low levels of <italic>MGRN1</italic> expression. Similarly, <italic>EGR1</italic> mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with <italic>MGRN1</italic> mRNA expression. Kaplan-Meier analyses showed that high methylation of the <italic>MGRN1</italic> promoter region and low expression of <italic>MGRN1</italic> were associated with worse survival of HGSOC patients. In multivariable models, low <italic>MGRN1</italic> expression was an independent factor predicting poor outcome. Furthermore, low expression of <italic>EGR1</italic> was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the <italic>MGRN1</italic> promoter region and low expression of <italic>MGRN1</italic> were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering <italic>EGR1</italic> expression.</p>