p38delta/MAPK13 as a diagnostic marker for cholangiocarcinoma and its involvement in cell motility and invasion.
Cholangiocarcinoma (CC) and hepatocellularcarcinoma (HCC) are two main forms of liver malignancies, which exhibit differences in drug response and prognosis. Immunohistotochemical staining for cytokeratin markers has been used to some success in the differential diagnosis of CC from HCC. However, there remains a need for additional markers for increased sensitivity and specificity of diagnosis. In this study, we have identified a p38 MAP kinase, p38delta (also known as MAPK13 or SAPK4) as a protein that is upregulated in CC relative to HCC and to normal biliary tract tissues. We performed microarray gene expression profiling on 17 cases of CC, 12 cases of adjacent normal liver tissue, and three case of normal bile duct tissue. p38delta was upregulated in 16 out of 17 cases of CC relative to normal tissue. We subsequently performed immunohistochemical staining of p38delta in 54 cases of CC and 54 cases of HCC. p38delta staining distinguished CC from HCC with a sensitivity of 92.6% and a specificity of 90.7%. To explore the possible functional significance of p38delta expression in CC, we examined the effects of overexpression and knockdown of p38delta expression in human CC cell lines. Our results indicate that p38delta is important for motility and invasion of CC cells, suggesting that p38delta may play an important role in CC metastasis. In summary, p38delta may serve as a novel diagnostic marker for CC and may also serve as a new target for molecular based therapy of this disease.
Tan
Felicia Li-Sher
FL
Department of General Surgery, Singapore General Hospital, Singapore.
Ooi
Aikseng
A
Huang
Dachuan
D
Wong
Jing Chii
JC
Qian
Chao-Nan
CN
Chao
Cora
C
Ooi
London
L
Tan
Yu-Meng
YM
Chung
Alexander
A
Cheow
Peng-Chung
PC
Zhang
Zhongfa
Z
Petillo
David
D
Yang
Ximing J
XJ
Teh
Bin Tean
BT
D000951:Antigens, Neoplasm / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003094:Collagen; D003937:Diagnosis, Differential; D004338:Drug Combinations; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007797:Laminin; D048292:Mitogen-Activated Protein Kinase 13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011509:Proteoglycans; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D048292:Mitogen-Activated Protein Kinase 13