Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma.
OBJECTIVE
Specific markers are required for early detection and diagnosis of intrahepatic cholangiocarcinoma (ICC); however, the tumour markers currently in use are not specific for ICC.


METHODS
We compared an ICC cDNA library with that of hepatocellular carcinoma (HCC) by serial analysis of gene expression (SAGE). The expression patterns in each were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemical analysis of 74 samples including 16 ICC samples.


RESULTS
A comparison of the two libraries revealed distinct gene expression patterns for each type of liver cancer. In addition to the known tumour markers, we detected nine novel genes associated with ICC. By comparing the mean transcript abundance in the ICC library with those in other libraries, including gastric, colon, prostate and breast cancer, together with our RT-PCR results, we identified three genes as specific markers of ICC: biglycan, insulin-like growth factor-binding protein 5 and claudin-4. Immunoblotting and immunohistochemical analyses showed that claudin-4 was highly expressed in ICC. Moreover, discrimination analysis revealed that a combination of these genes could be used to distinguish ICC from HCC or metastatic adenocarcinoma.


CONCLUSIONS
We identified novel marker genes of ICC that are potentially useful for the diagnosis of liver cancer.
Nishino
Ryuhei
R
Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8641, Japan.
Honda
Masao
M
Yamashita
Taro
T
Takatori
Hajime
H
Minato
Hiroshi
H
Zen
Yoh
Y
Sasaki
Motoko
M
Takamura
Hiroyuki
H
Horimoto
Katsuhisa
K
Ohta
Tetsuo
T
Nakanuma
Yasuni
Y
Kaneko
Shuichi
S
D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor