Promoter methylation of SFRPs gene family in cervical cancer

Ming Tzeung Chung, Huey Kang Sytwu, Ming D. Yan, Yu Lueng Shih, Cheng Chang Chang, Mu Hsien Yu, Tang Yuan Chu, Hung Cheng Lai, Ya W. Lin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objectives: Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear. Methods: The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls. Results: The SFRP1 promoter was hypermethylated in 33.9% of SCC, 8.2% of HSIL, 2.2% of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7% of SCC, 16.3% of HSIL, 15.6% LSIL and 4.4% normal tissues. The SFRP4 promoter was hypermethylated in 67.9% of SCC, 36.7% of HSIL, 4.4% of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1% of SCC, 4.1% of HSIL, 13.3% of LSIL and 4.4% normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P <0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0% vs 15.2%, respectively, P <0.05). Conclusions: Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalGynecologic Oncology
Volume112
Issue number2
DOIs
Publication statusPublished - Feb 2009
Externally publishedYes

Fingerprint

Uterine Cervical Neoplasms
Methylation
Genes
Squamous Cell Carcinoma
Neoplasms
Squamous Intraepithelial Lesions of the Cervix
FRZB protein
Carcinogenesis
Catenins
Wnt Signaling Pathway
Lymph Nodes
Neoplasm Metastasis
Cell Line

Keywords

  • Cervical cancer
  • Epigenetic inactivation
  • SFRP genes

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Chung, M. T., Sytwu, H. K., Yan, M. D., Shih, Y. L., Chang, C. C., Yu, M. H., ... Lin, Y. W. (2009). Promoter methylation of SFRPs gene family in cervical cancer. Gynecologic Oncology, 112(2), 301-306. https://doi.org/10.1016/j.ygyno.2008.10.004

Promoter methylation of SFRPs gene family in cervical cancer. / Chung, Ming Tzeung; Sytwu, Huey Kang; Yan, Ming D.; Shih, Yu Lueng; Chang, Cheng Chang; Yu, Mu Hsien; Chu, Tang Yuan; Lai, Hung Cheng; Lin, Ya W.

In: Gynecologic Oncology, Vol. 112, No. 2, 02.2009, p. 301-306.

Research output: Contribution to journalArticle

Chung, MT, Sytwu, HK, Yan, MD, Shih, YL, Chang, CC, Yu, MH, Chu, TY, Lai, HC & Lin, YW 2009, 'Promoter methylation of SFRPs gene family in cervical cancer', Gynecologic Oncology, vol. 112, no. 2, pp. 301-306. https://doi.org/10.1016/j.ygyno.2008.10.004
Chung MT, Sytwu HK, Yan MD, Shih YL, Chang CC, Yu MH et al. Promoter methylation of SFRPs gene family in cervical cancer. Gynecologic Oncology. 2009 Feb;112(2):301-306. https://doi.org/10.1016/j.ygyno.2008.10.004
Chung, Ming Tzeung ; Sytwu, Huey Kang ; Yan, Ming D. ; Shih, Yu Lueng ; Chang, Cheng Chang ; Yu, Mu Hsien ; Chu, Tang Yuan ; Lai, Hung Cheng ; Lin, Ya W. / Promoter methylation of SFRPs gene family in cervical cancer. In: Gynecologic Oncology. 2009 ; Vol. 112, No. 2. pp. 301-306.
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abstract = "Objectives: Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear. Methods: The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls. Results: The SFRP1 promoter was hypermethylated in 33.9{\%} of SCC, 8.2{\%} of HSIL, 2.2{\%} of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7{\%} of SCC, 16.3{\%} of HSIL, 15.6{\%} LSIL and 4.4{\%} normal tissues. The SFRP4 promoter was hypermethylated in 67.9{\%} of SCC, 36.7{\%} of HSIL, 4.4{\%} of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1{\%} of SCC, 4.1{\%} of HSIL, 13.3{\%} of LSIL and 4.4{\%} normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P <0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0{\%} vs 15.2{\%}, respectively, P <0.05). Conclusions: Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.",
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AU - Yan, Ming D.

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AU - Chang, Cheng Chang

AU - Yu, Mu Hsien

AU - Chu, Tang Yuan

AU - Lai, Hung Cheng

AU - Lin, Ya W.

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N2 - Objectives: Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear. Methods: The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls. Results: The SFRP1 promoter was hypermethylated in 33.9% of SCC, 8.2% of HSIL, 2.2% of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7% of SCC, 16.3% of HSIL, 15.6% LSIL and 4.4% normal tissues. The SFRP4 promoter was hypermethylated in 67.9% of SCC, 36.7% of HSIL, 4.4% of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1% of SCC, 4.1% of HSIL, 13.3% of LSIL and 4.4% normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P <0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0% vs 15.2%, respectively, P <0.05). Conclusions: Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.

AB - Objectives: Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear. Methods: The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls. Results: The SFRP1 promoter was hypermethylated in 33.9% of SCC, 8.2% of HSIL, 2.2% of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7% of SCC, 16.3% of HSIL, 15.6% LSIL and 4.4% normal tissues. The SFRP4 promoter was hypermethylated in 67.9% of SCC, 36.7% of HSIL, 4.4% of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1% of SCC, 4.1% of HSIL, 13.3% of LSIL and 4.4% normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P <0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0% vs 15.2%, respectively, P <0.05). Conclusions: Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.

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