Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma.
Pancreatic ductal carcinoma (PDC) is one of the most intractable human malignancies. Surgical resection of PDC at curable stages is hampered by a lack of sensitive and reliable detection methods. Given that DNA microarray analysis allows the expression of thousands of genes to be monitored simultaneously, it offers a potentially suitable approach to the identification of molecular markers for the clinical diagnosis of PDC. However, a simple comparison between the transcriptomes of normal and cancerous pancreatic tissue is likely to yield misleading pseudopositive data that reflect mainly the different cellular compositions of the specimens. Indeed, a microarray comparison of normal and cancerous tissue identified the INSULIN gene as one of the genes whose expression was most specific to normal tissue. To eliminate such a "population-shift" effect, the pancreatic ductal epithelial cells were purified by MUC1-based affinity chromatography from pancreatic juice isolated from both healthy individuals and PDC patients. Analysis of these background-matched samples with DNA microarrays representing 3456 human genes resulted in the identification of candidate genes for PDC-specific markers, including those for AC133 and carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7). Specific expression of these genes in the ductal cells of the patients with PDC was confirmed by quantitative real-time polymerase chain reaction analysis. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC that relies on pancreatic juice, which is routinely obtained in the clinical setting.
Yoshida
Koji
K
Division of Functional Genomics, Jichi Medical School, Kawachi-gun, Tochigi.
Ueno
Shuichi
S
Iwao
Toshiyasu
T
Yamasaki
Souichirou
S
Tsuchida
Akira
A
Ohmine
Ken
K
Ohki
Ruri
R
Choi
Young Lim
YL
Koinuma
Koji
K
Wada
Tomoaki
T
Ota
Jun
J
Yamashita
Yoshihiro
Y
Chayama
Kazuaki
K
Sato
Kazuhiro
K
Mano
Hiroyuki
H
D001483:Base Sequence; D044584:Carcinoma, Ductal / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002760:Cholangiopancreatography, Endoscopic Retrograde; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010183:Pancreatic Ducts / Q000473:pathology*; D010189:Pancreatic Juice / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012016:Reference Values
D017931:DNA Primers