PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma.
The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients.
He
Furong
F
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Yan
Qingguo
Q
Fan
Linni
L
Liu
Yixiong
Y
Cui
Jihong
J
Wang
Juanhong
J
Wang
Lu
L
Wang
Yingmei
Y
Wang
Zhe
Z
Guo
Ying
Y
Huang
Gaosheng
G
D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D003937:Diagnosis, Differential; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase