Hypermethylation and aberrant expression of secreted frizzled-related protein genes in pancreatic cancer.
OBJECTIVE
To determine the methylation status and aberrant expression of some secreted frizzled-related protein (SFRP) genes in pancreatic cancer and explore their role in pancreatic carcinogenesis.


METHODS
Methylation status and expression of SFRP genes were detected by methylation-specific PCR (MSPCR) and reverse-transcription PCR (RT-PCR) respectively.


RESULTS
The frequencies of methylation for SFRP genes 1, 2, 4, 5 were 70%, 48.3%, 60% and 76.7% in pancreatic cancer samples, and 21.7%, 20%, 10% and 36.7% in matched cancer adjacent normal tissue samples, respectively (c2 = 28.23, P < 0.0001 for SFRP gene 1; c2 = 10.71, P = 0.001 for SFRP gene 2; c2 = 32.97, P < 0.0001 for SFRP gene 4; c2 = 19.55, P < 0.0001 for SFRP gene 5). Expression loss of SFRP genes 1, 2, 4 and 5 was found in 65%, 40%, 55% and 71.7% of 60 pancreatic cancer samples, and 25%, 15%, 18.3% and 31.7% of matched cancer adjacent normal tissue samples, respectively (c2 = 19.39, P < 0.0001 for SFRP gene 1; c2 = 9.40, P = 0.002 for SFRP gene 2; c2 = 17.37, P < 0.0001 for SFRP gene 4; c2 = 19.22, P < 0.0001 for SFRP gene 5). SFRP gene 1 was methylated but not expressed in PC-3 and PANC-1, SFRP gene 2 was methylated but not expressed in PANC-1 and CFPAC-1, SFRP gene 4 was methylated but not expressed in PC-3, and SFRP gene 5 was methylated but not expressed in CFPAC-1.


CONCLUSIONS
Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer, which may be involved in pancreatic carcino-genesis.
Bu
Xian-Min
XM
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Zhao
Cheng-Hai
CH
Zhang
Ning
N
Gao
Feng
F
Lin
Shuai
S
Dai
Xian-Wei
XW
D048868:Adaptor Proteins, Signal Transducing; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D005136:Eye Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; 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