RRC ID 42754
著者 Jiang P, Watanabe H, Okada G, Ohtsubo K, Mouri H, Tsuchiyama T, Yao F, Sawabu N.
タイトル Diagnostic utility of aberrant methylation of tissue factor pathway inhibitor 2 in pure pancreatic juice for pancreatic carcinoma.
ジャーナル Cancer Sci
Abstract The tissue factor pathway inhibitor 2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor. Recently, the aberrant methylation of TFPI-2 was detected frequently in pancreatic carcinoma (PCa) tissues but not in normal pancreatic tissues. We analyzed the aberrant methylation of TFPI-2 in the pure pancreatic juice (PPJ) aspirated endoscopically from patients with various pancreatic diseases. Using the highly sensitive methylation-specific polymerase chain reaction (MSP) and quantitative MSP (Q-MSP) assay, we investigated the aberrant methylation of TFPI-2 in nine human PCa cell lines and in the PPJ from patients with PCa, intraductal papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP). The incidence of aberrant TFPI-2 methylation was seven (77.8%) of nine PCa cell lines by Q-MSP. In cell lines, the expression of TFPI-2 mRNA by quantitative reverse transcription-polymerase chain reaction showed an inverse correlation to the aberrant methylation of TFPI-2. The incidence of aberrant TFPI-2 methylation in the PPJ was 21 (58.3%) of 36 PCa patients, three (17.6%) of 17 IPMN and one (4.8%) of 21 CP by MSP assay. Using a suitable cut-off value of 2.5 according to the receiver operating characteristic curve, the incidence of aberrant TFPI-2 methylation in the PPJ by real-time MSP was 18 (62.1%) of 29 PCa patients, one (5.1%) of 17 IPMN and three (14.3%) of 21 CP, respectively. The incidence of quantitative TFPI-2 hypermethylation in the PPJ with PCa was significantly higher than that with IPMN (P < 0.001) or CP (P < 0.001). Moreover, the aberrant methylation rate of TFPI-2 in the PPJ was 100%, as observed (6/6) in the PCa patients with liver metastasis, and 86.7% (26/30) in stages IVa + IVb of PCa by Q-MSP assay. These results suggest that promoter methylation of TFPI-2 in the PPJ may be a useful marker in the diagnosis and progression of PCa using an endoscopically feasible approach.
巻・号 97(11)
ページ 1267-73
公開日 2006-11-1
DOI 10.1111/j.1349-7006.2006.00308.x
PII CAS308
PMID 16965396
MeSH Adenocarcinoma, Mucinous / diagnosis Adenocarcinoma, Mucinous / genetics Aged Antimetabolites, Antineoplastic / pharmacology Azacitidine / pharmacology Carcinoma, Pancreatic Ductal / diagnosis Carcinoma, Pancreatic Ductal / genetics Carcinoma, Papillary / diagnosis Carcinoma, Papillary / genetics Cell Line, Tumor DNA Methylation* DNA, Neoplasm / genetics DNA, Neoplasm / metabolism Female Gene Expression Regulation, Neoplastic Glycoproteins / genetics* Humans Male Middle Aged Pancreatic Juice / metabolism* Pancreatic Neoplasms / diagnosis* Pancreatic Neoplasms / genetics* Pancreatitis, Chronic / genetics Pancreatitis, Chronic / pathology Polymerase Chain Reaction Promoter Regions, Genetic RNA, Neoplasm / genetics RNA, Neoplasm / metabolism Reverse Transcriptase Polymerase Chain Reaction
IF 4.966
引用数 22
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MIA Paca2(RCB2094)