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

作者：Ho Chih Ming; Huang Chi Jung; Huang Chia Yen; Wu Yih Yiing; Chang Shwu Fen^*; Cheng Wen Fang

来源：Molecular Cancer, 2012, 11: 53.

DOI：10.1186/1476-4598-11-53

• Ovarian clear cell adenocarcinoma
• Methylation-specific multiplex ligation-dependent probe amplification
• HIN-1
• CACNA1A

Background: 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). %26lt;br%26gt;Materials and methods: 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. %26lt;br%26gt;Results: 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. 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%, p = 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. %26lt;br%26gt;Conclusions: 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.

• 出版日期2012-8-8
• 单位河北医科大学