Application of Multiplex Nested Methylated Specific PCR in Early Diagnosis of Epithelial Ovarian Cancer

Abstract

Objective: To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Materials and Methods: Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). Results: The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Conclusions: Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…In a more recent study by Wang et al, a multiplex-nested MSP was also developed for the detection of three genes methylation in 114 serum cfDNA of epithelial ovarian cancer patients. cfDNA methylation levels were significantly increased in ovarian cancer patients compared to benign disease patients and healthy control groups [70].…”

Loss of opioid binding protein/cell adhesion molecule‑like gene expression in gastric cancer

“…DNA methylation is an epigenetic phenomenon that affects gene expression without altering the DNA sequence (20)(21)(22)(23)(24). Aberrant supermethylation occurs in promoter CpG islands, and is a mechanism by which tumor suppressor genes are silenced and, in certain circumstance, may be an important mechanism (20)(21)(22)(23)(24).…”

OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis

“…The cases comprised of cancer tissues and blood from ovarian cancer patients. Among the eight included studies, six studies clearly described that the cases were primary tumor patients whereas two studies (Wang et al, 2015;Xing et al, 2015) did not. In the study performed by Liu et al (2008), there are 41 metastatic tissues of pelvic and abdomen cavity.…”

“…Many studies have indicated that OPCML DNA hypermethylation frequently occurs in ovarian cancers. However, the findings remain unclear regarding the small population and different methods in previous studies (Czekierdowski et al, 2006;Zhang et al, 2006Zhang et al, , 2014Chen et al, 2007;Liu et al, 2008;Zhou et al, 2011Zhou et al, , 2014aWang et al, 2015Wang et al, , 2017Xing et al, 2015). Therefore, we performed a meta-analysis to identify the association of OPCML methylation with ovarian cancer risk.…”