Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Abstract

ABSTRACT. DNA methylation plays an important role in carcinogenesis and cancer development. In this study, we examined gene methylation in epithelial ovarian cancer (EOC) using cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) to evaluate the application of cumulative methylation alternations of genes associated with cancer antigen 125 for early cancer diagnosis. The methylation status of 3 genes (Ras association domain family 1 isoform A, RASSF1A; opioid-binding protein/cell adhesion molecule, OPCML; homeobox A9, HOXA9) were examined and compared in 35 EOC samples and 11 normal ovarian tissue samples using CCP-based FRET. Gene methylation levels were clustered into 3 sections and assigned a value; values for the 3 genes were summed. Although methylation of the OPCML gene was significantly associated with stage, histological types, grade, and ascites and that of RASSF1A and HOXA9 was not, the sum for the 3 genes was significantly associated with stage and ascites. The sum showed higher sensitivity (85.7%) and specificity (100%) for discriminating EOC from normal ovarian tissues than did the methylation status of RASSF1A, OPCML, and HOXA9

Serum cell-free DNA methylation of OPCML and HOXD9 as a biomarker that may aid in differential diagnosis between cholangiocarcinoma and other biliary diseases

“…As circulating cfDNA may reflect the characteristics of the primary tumor and even of metastatic tumor in real time, it may be an excellent biomarker for cancer patients [20]. Evaluation of OPCML methylation as a diagnostic biomarker in clinical tissue samples has been performed in ovarian cancer [63], cholangiocarcinoma [64], prostate cancer [65], and lung cancer [27]. With the advent of liquid biopsy, it becomes superior to tissue biopsy because of its less invasiveness and clinically practical method.…”

Identification of a Robust Methylation Classifier for Cutaneous Melanoma Diagnosis

“…FLJ22536, recently identified as CASC15, is a putative mediator of neural growth and differentiation and a tumor suppressor in neuroblastoma (Russell et al, 2015), and in melanoma it is linked to disease progression and phenotype switching between proliferative and invasive states (Lessard et al, 2015). Other diagnostic genes lack well-defined roles in melanoma; however, in other cancer types, a number exhibit aberrant expression (Gao et al, 2015;Jiang et al, 2008;Makiyama et al, 2005) and/or methylation (Jones et al, 2013;Kikuchi et al, 2013;Lai et al, 2008;Li et al, 2015;Semaan et al, 2016;Song et al, 2015;Wimmer et al, 2002 GSE45266 validation set -27K methylation differentiation (Zha et al, 2012), or are diagnostic (Semaan et al, 2016;Song et al, 2015;Xing et al, 2015), prognostic (Dietrich et al, 2013;Galluzzi et al, 2013;Qiu et al, 2015;Zheng et al, 2015;Zhou et al, 2014), or predictive biomarkers (Tada et al, 2011). Our 40-CpG classifier for melanoma diagnosis may have advantages over other available approaches for melanoma diagnosis.…”

Relationship between RAS Association Domain Family Protein 1A Promoter Methylation and the Clinicopathological Characteristics in Patients with Ovarian Cancer: A Systematic Meta-Analysis

“…Of the included studies, 6 studies analyzed the relationship between RASSF1A promoter methylation and ovarian cancer in cancer versus LMP tumors [22, 31, 36, 37, 40,  41]. Sixteen studies analyzed the correlation of ­ RASSF1A promoter methylation with clinicopathological features in ovarian cancer [19, 22, 28-31, 33-42]. Two studies recorded the prognostic role of RASSF1A promoter methylation on patients with ovarian cancer [32, 33].…”

“…According to the selection criteria, eventually, 17 eligible publications with 1,108 ovarian cancer samples [19, 22, 28-42] were identified in this meta-analysis (Fig. 1).…”