Integrative Analysis of Gene Expression and Promoter Methylation to Differentiate High-Grade Serous Ovarian Cancer from Benign Tumors

<b>Background:</b> Ovarian cancer (OC) is the third most common and second most lethal onco-gynecological disease in the world, with high-grade serous ovarian cancer (HGSOC) making up the majority of OC cases worldwide. The current serological biomarkers used for OC diagnosis are lacking sensitivity and specificity, thus new biomarkers are greatly needed. Recently, the chromatin remodeling complex gene <i>ARID1A</i>, Notch and Wnt pathway gene expression, as well as <i>HOX</i>-related gene promoter methylation have been linked with promoting OC. <b>Methods:</b> In this pilot study, 10 gene expression biomarkers and 4 promoter methylation biomarkers were examined as potential diagnostic and prognostic indicators of OC in 65 fresh-frozen gynecologic tumor tissues. <b>Results:</b> Out of 10 genes analyzed, the expression of eight biomarkers was significantly reduced in OC cases compared to benign, and <i>HOX</i>-related gene promoter methylation significantly increased in OC tumors. Out of 14 biomarkers, <i>CTNNB1</i> showed the best single biomarker separation of HGSOC from benign cases (AUC = 0.97), while a combination of the seven Notch pathway-related gene expressions (<i>NOTCH1</i>, <i>NOTCH2</i>, <i>NOTCH3</i>, <i>NOTCH4</i>, <i>DLL1</i>, <i>JAG2</i>, and <i>HES1</i>) demonstrated the best separation of HGSOC from the benign cases (AUC = 1). <b>Conclusions:</b> The combination of multiple gene expression or gene promoter methylation biomarkers shows great promise for the development of an effective biomarker-based diagnostic approach for OC.