Promoter methylation of sFRP5 in patients with ovarian clear cell adenocarcinomaARTICLE

Chih Ming Ho, Hung Cheng Lai, Shih Hung Huang, Tsai Yen Chien, Ming Chieh Lin, Shwu Fen Chang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Specific tumour suppressor genes with promoter methylation in ovarian clear cell adenocarcinoma (OCCA) can be one important epigenetic mark distinguishing OCCA from ovarian serous adenocarcinoma (OSA), benign endometriotic cysts and normal ovarian epitheliums. Materials and methods Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14ARF, p15INK4b, p16 INK4a and survivin. Methylation frequencies of identified targets were further analysed with individual DNA samples. Results The sFRP5 promoter was significantly methylated in all OCCA cell lines, with 64·6% in OCCA tissues compared with 13·3% in OSA, and 0% in benign endometriotic cysts and normal ovarian epitheliums (P <0·0001). With a median follow-up of 44 months, the expected 5-year overall survival (OS) for patients with methylated sFRP5 promoter were significantly worse than for those with unmethylated sFRP5 (52% vs. 88%, P = 0·03). After adjusting for age, stage, and residual disease after primary surgery, patients with unmethylated sFRP5 promoter had an independent good prognostic factor in OS (P = 0·017). Conclusion The high percentage of promoter methylation in the sFRP5 gene in OCCA indicates its importance in the development of OCCA and is a potential useful marker for prognoses and target for treatment of OCCA.

Original languageEnglish
Pages (from-to)310-318
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume40
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Clear Cell Adenocarcinoma
Methylation
Genes
Tumor Suppressor Protein p14ARF
Cells
Tissue
Ovarian Cysts
Adenocarcinoma
Retinoblastoma Protein
DNA
Surgery
Adenomatous Polyposis Coli Protein
Tumors
Naphazoline
Cell Line
Survival
Neoplasm Genes
Tumor Suppressor Genes
Epigenomics
Cysts

Keywords

  • MS-PCR
  • Ovarian clear cell adenocarcinoma
  • Promoter methylation

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Biochemistry
  • Biochemistry

Cite this

Promoter methylation of sFRP5 in patients with ovarian clear cell adenocarcinomaARTICLE. / Ho, Chih Ming; Lai, Hung Cheng; Huang, Shih Hung; Chien, Tsai Yen; Lin, Ming Chieh; Chang, Shwu Fen.

In: European Journal of Clinical Investigation, Vol. 40, No. 4, 04.2010, p. 310-318.

Research output: Contribution to journalArticle

Ho, Chih Ming ; Lai, Hung Cheng ; Huang, Shih Hung ; Chien, Tsai Yen ; Lin, Ming Chieh ; Chang, Shwu Fen. / Promoter methylation of sFRP5 in patients with ovarian clear cell adenocarcinomaARTICLE. In: European Journal of Clinical Investigation. 2010 ; Vol. 40, No. 4. pp. 310-318.
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abstract = "Background Specific tumour suppressor genes with promoter methylation in ovarian clear cell adenocarcinoma (OCCA) can be one important epigenetic mark distinguishing OCCA from ovarian serous adenocarcinoma (OSA), benign endometriotic cysts and normal ovarian epitheliums. Materials and methods Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14ARF, p15INK4b, p16 INK4a and survivin. Methylation frequencies of identified targets were further analysed with individual DNA samples. Results The sFRP5 promoter was significantly methylated in all OCCA cell lines, with 64·6{\%} in OCCA tissues compared with 13·3{\%} in OSA, and 0{\%} in benign endometriotic cysts and normal ovarian epitheliums (P <0·0001). With a median follow-up of 44 months, the expected 5-year overall survival (OS) for patients with methylated sFRP5 promoter were significantly worse than for those with unmethylated sFRP5 (52{\%} vs. 88{\%}, P = 0·03). After adjusting for age, stage, and residual disease after primary surgery, patients with unmethylated sFRP5 promoter had an independent good prognostic factor in OS (P = 0·017). Conclusion The high percentage of promoter methylation in the sFRP5 gene in OCCA indicates its importance in the development of OCCA and is a potential useful marker for prognoses and target for treatment of OCCA.",
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AU - Ho, Chih Ming

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AU - Lin, Ming Chieh

AU - Chang, Shwu Fen

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N2 - Background Specific tumour suppressor genes with promoter methylation in ovarian clear cell adenocarcinoma (OCCA) can be one important epigenetic mark distinguishing OCCA from ovarian serous adenocarcinoma (OSA), benign endometriotic cysts and normal ovarian epitheliums. Materials and methods Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14ARF, p15INK4b, p16 INK4a and survivin. Methylation frequencies of identified targets were further analysed with individual DNA samples. Results The sFRP5 promoter was significantly methylated in all OCCA cell lines, with 64·6% in OCCA tissues compared with 13·3% in OSA, and 0% in benign endometriotic cysts and normal ovarian epitheliums (P <0·0001). With a median follow-up of 44 months, the expected 5-year overall survival (OS) for patients with methylated sFRP5 promoter were significantly worse than for those with unmethylated sFRP5 (52% vs. 88%, P = 0·03). After adjusting for age, stage, and residual disease after primary surgery, patients with unmethylated sFRP5 promoter had an independent good prognostic factor in OS (P = 0·017). Conclusion The high percentage of promoter methylation in the sFRP5 gene in OCCA indicates its importance in the development of OCCA and is a potential useful marker for prognoses and target for treatment of OCCA.

AB - Background Specific tumour suppressor genes with promoter methylation in ovarian clear cell adenocarcinoma (OCCA) can be one important epigenetic mark distinguishing OCCA from ovarian serous adenocarcinoma (OSA), benign endometriotic cysts and normal ovarian epitheliums. Materials and methods Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14ARF, p15INK4b, p16 INK4a and survivin. Methylation frequencies of identified targets were further analysed with individual DNA samples. Results The sFRP5 promoter was significantly methylated in all OCCA cell lines, with 64·6% in OCCA tissues compared with 13·3% in OSA, and 0% in benign endometriotic cysts and normal ovarian epitheliums (P <0·0001). With a median follow-up of 44 months, the expected 5-year overall survival (OS) for patients with methylated sFRP5 promoter were significantly worse than for those with unmethylated sFRP5 (52% vs. 88%, P = 0·03). After adjusting for age, stage, and residual disease after primary surgery, patients with unmethylated sFRP5 promoter had an independent good prognostic factor in OS (P = 0·017). Conclusion The high percentage of promoter methylation in the sFRP5 gene in OCCA indicates its importance in the development of OCCA and is a potential useful marker for prognoses and target for treatment of OCCA.

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