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

Chih Ming Ho, Chi Jung Huang, Chia Yen Huang, Yih Yiing Wu, Shwu Fen Chang, Wen Fang Cheng

研究成果: 雜誌貢獻文章

19 引文 (Scopus)

摘要

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). 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. 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 5-year PFS and OS for patients with methylated promoters of HIN-1 and CACNA1A genes were significantly worse than those for patients without methylated HIN-1 (28% vs. 54%, p = 0.047 for PFS; 30% vs. 62%, p = 0.002 for OS, respectively) and CACNA1A (30% vs. 63%, p=0.01 for PFS; 40% vs. 75%, p=0.02 for OS). When 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. Conclusions: Methylation of HIN-1 and CACNA1A promoters are two novel epigenetic biomarkers associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity through Akt pathway.

原文英語
頁(從 - 到)53
頁數1
期刊Molecular Cancer
DOIs
出版狀態接受/付印 - 八月 8 2012
對外發佈Yes

指紋

Clear Cell Adenocarcinoma
Methylation
Genes
Multiplex Polymerase Chain Reaction
Paclitaxel
Far-Western Blotting
Apoptosis
Carcinoma
Caspase 7
Ovarian Cysts
Tumor Suppressor Genes
Epigenomics
Caspase 3
Cysts
Biomarkers
Phosphorylation
Cell Line
Growth

ASJC Scopus subject areas

  • Oncology
  • Molecular Medicine
  • Cancer Research

引用此文

Promoter Methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma. / Ho, Chih Ming; Huang, Chi Jung; Huang, Chia Yen; Wu, Yih Yiing; Chang, Shwu Fen; Cheng, Wen Fang.

於: Molecular Cancer, 08.08.2012, p. 53.

研究成果: 雜誌貢獻文章

Ho, Chih Ming ; Huang, Chi Jung ; Huang, Chia Yen ; Wu, Yih Yiing ; Chang, Shwu Fen ; Cheng, Wen Fang. / Promoter Methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma. 於: Molecular Cancer. 2012 ; 頁 53.
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title = "Promoter Methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma",
abstract = "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). 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. 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 5-year PFS and OS for patients with methylated promoters of HIN-1 and CACNA1A genes were significantly worse than those for patients without methylated HIN-1 (28{\%} vs. 54{\%}, p = 0.047 for PFS; 30{\%} vs. 62{\%}, p = 0.002 for OS, respectively) and CACNA1A (30{\%} vs. 63{\%}, p=0.01 for PFS; 40{\%} vs. 75{\%}, p=0.02 for OS). When 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. Conclusions: Methylation of HIN-1 and CACNA1A promoters are two novel epigenetic biomarkers associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity through Akt pathway.",
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AU - Ho, Chih Ming

AU - Huang, Chi Jung

AU - Huang, Chia Yen

AU - Wu, Yih Yiing

AU - Chang, Shwu Fen

AU - Cheng, Wen Fang

PY - 2012/8/8

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N2 - 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). 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. 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 5-year PFS and OS for patients with methylated promoters of HIN-1 and CACNA1A genes were significantly worse than those for patients without methylated HIN-1 (28% vs. 54%, p = 0.047 for PFS; 30% vs. 62%, p = 0.002 for OS, respectively) and CACNA1A (30% vs. 63%, p=0.01 for PFS; 40% vs. 75%, p=0.02 for OS). When 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. Conclusions: Methylation of HIN-1 and CACNA1A promoters are two novel epigenetic biomarkers associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity through Akt pathway.

AB - 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). 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. 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 5-year PFS and OS for patients with methylated promoters of HIN-1 and CACNA1A genes were significantly worse than those for patients without methylated HIN-1 (28% vs. 54%, p = 0.047 for PFS; 30% vs. 62%, p = 0.002 for OS, respectively) and CACNA1A (30% vs. 63%, p=0.01 for PFS; 40% vs. 75%, p=0.02 for OS). When 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. Conclusions: Methylation of HIN-1 and CACNA1A promoters are two novel epigenetic biomarkers associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity through Akt pathway.

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