Promoter Methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma

• Main Authors: Ho Chih-Ming, Huang Chi-Jung, Huang Chia-Yen, Wu Yih-Yiing, Chang Shwu-Fen, Cheng Wen-Fang
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: Molecular Cancer
• Subjects: Ovarian clear cell adenocarcinoma; Methylation-specific multiplex ligation-dependent probe amplification; HIN-1; CACNA1A
• Online Access: http://www.molecular-cancer.com/content/11/1/53

<p>Abstract</p> <p>Background</p> <p>This study is to analyze promoter methylation of various tumor suppressor genes in different types of ovarian carcinoma and to identify potential therapeutic targets of ovarian clear cell adenocarcinoma (OCCA).</p> <p>Materials and methods</p> <p>The promoter methylation statuses of 40 genes in primary ovarian carcinomas including 47 clear- and 63 non-clear-cell type tissues, 6 OCCA cell lines, 29 benign ovarian endometriotic cysts, and 31 normal controls were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The MS-MLPA results were correlated with clinicopathological features and outcomes of 47 OCCA patients. Functions of the target genes were further explored by Western Blot Analysis, apoptosis assay, and caspase-3/7 activity analysis.</p> <p>Results</p> <p>Frequencies of methylated RASSF1A, CDH13, CACNA1A, HIN-1, and sFRP5 genes in OCCA tissues were significantly higher than those in non-OCCA cancerous tissues and benign endometriotic cysts<b>.</b> The expected OS for patients with methylated promoters of HIN-1 was significantly worse than those for patients without methylated HIN-1 (30% vs. 62%, <it>p</it> = 0.002). The HIN-1 gene was over-expressed in ES2 cells, a significant reduction in cell growth and induction of apoptosis, and increasing paclitaxel sensitivity by reducing phosphorylation of Akt were observed.</p> <p>Conclusions</p> <p>Methylation of HIN-1 promoter is a novel epigenetic biomarker associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity which is partly through Akt pathway.</p>