An epigenetic marker panel for screening and prognostic prediction of ovarian cancer

Aberrant CpG island hypermethylation is a common finding of cancers, which might be detectable in the tissue or serum of affected patients. We analyzed DNA methylation by methylation‐specific polymerase chain reaction of 7 genes, which included secreted frizzled receptor proteins 1, 2, 4, 5 ( SFRP1, 2, 4, 5 ), SRY‐box 1 ( SOX1 ), paired box gene 1 ( PAX1 ) and LIM homeobox transcription factor 1, alpha ( LMX1A ) in primary tumor samples from 126 patients with ovarian cancer, 75 with a benign tumor and 14 with borderline malignancy of an ovarian tumor, and in the serum from 26 patients with ovarian cancer and 20 with a benign tumor. Six of 7 genes had higher methylation rates in patients with ovarian cancer than in borderline malignancy or benign tumor ( p < 0.001). The methylation of SFRP1 , SFRP2 , SOX1 and LMX1A genes correlated with recurrence and overall survival of ovarian cancer patients. Combining the data for SFRP1, SFRP2 and SOX1 genes gave a relative risk for recurrence of 3.19 ( p = 0.013) in patients with at least one gene methylation, and combining the data for SFRP1, SOX1 and LMX1A gave an RR for cancer‐related death of 6.09 ( p = 0.010). Methylation analysis of tissues and serum revealed a significant correlation (kappa values, 0.332–0.598) and a highly sensitivity and specificity rates (73.08 and 75%) as a screening marker. In conclusion, promoter hypermethylation of specific genes in critical pathways is common in ovarian cancer and has potential as a prognostic factor and a promising serum marker for early screening. © 2008 Wiley‐Liss, Inc.