Abstract
To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). 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). 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). 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.
Highlights
Ovarian carcinoma is one of the malignant tumors commonly seen in women with mortality being 63.08%, ranking the first of malignant tumors in female reproductive system in China (Wang et al, 2014)
Serum free deoxyribose nucleic acid (DNA) methylation can be used as a biological marker for epithelial ovarian carcinoma (EOC) and multiplex nested methylated specific polymerase chain reaction (PCR) should be considered for early diagnosis since it can accurately determine tumor methylation conditions
Early diagnosis is of great significance in improving the prognosis and reducing the mortality of patients with ovarian carcinoma
Summary
Ovarian carcinoma is one of the malignant tumors commonly seen in women with mortality being 63.08%, ranking the first of malignant tumors in female reproductive system in China (Wang et al, 2014) It accounts for 3% of all female cancer-deaths, in which above 90% is caused by epithelial ovarian carcinoma (EOC) (Siegel et al, 2013). EOC is consisted of tumors with a series of biological behaviors and different pathological patterns, which can be divided into low-level carcinomas and highlevel carcinomas (Shih et al, 2004) The former, which include low-level clear cell carcinoma (CCC), low-level serous carcinoma, low-level endometrioid carcinoma and low-level mucinous carcinoma, etc., have distinctive genetic features in different pathological patterns and are slow in clinical development and favorable in prognosis. There is no simple and effective diagnostic method that can be routinely applied for the early diagnosis of EOC in clinic due to its complex pathological and clinical molecular biological characteristics (Pothuri et al, 2010)
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