Promoter methylation of SFRPs gene family in cervical cancer.
OBJECTIVE
Oncogenic activation of the Wnt/beta-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.
Chung
Ming-Tzeung
MT
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Sytwu
Huey-Kang
HK
Yan
Ming-De
MD
Shih
Yu-Lueng
YL
Chang
Cheng-Chang
CC
Yu
Mu-Hsien
MH
Chu
Tang-Yuan
TY
Lai
Hung-Cheng
HC
Lin
Ya-Wen
YW
D048868:Adaptor Proteins, Signal Transducing; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C109618:SFRP2 protein, human; C118723:SFRP4 protein, human; C118511:SFRP5 protein, human