title: JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC based on the molecular signature is not well-established.
  
  
  RESULTS
  In the present study, we reported HCC signature genes based on the JNK1 activation status in 31 HCC specimens relative to the matched distal noncancerous liver tissue from 31 patients. The HCCs with high JNK1 (H-JNK1) and low JNK1 (L-JNK1) were sub-grouped. Two different signature gene sets for both H-JNK1 and L-JNK1 HCC were identified through gene expression profiling. A striking overlap of signature genes was observed between the H-JNK1 HCC and the hepatoblastoma or hepatoblastoma-type HCC. Many established biomarkers for hepatic progenitor cells were over-expressed in H-JNK1 HCC, including AFP, TACSTD1, KRT19, KRT7, THY1, and PROM1. In addition, the majority of the most up-regulated genes were those associated with metastasis and earlier recurrence, whereas the genes for normal liver function were substantially down-regulated in H-JNK1 HCC tissue. A Kaplan-Meier plot demonstrated that the survival of the patients with H-JNK1 HCC was severely impaired.
  
  
  CONCLUSIONS
  Accordingly, we believe that the H-JNK1 HCC may originate from hepatic progenitor cells and is associated with poorer prognosis. The status of JNK1 activation in HCC tissue, thus, might be a new biomarker for HCC prognosis and therapeutic targeting.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY40536, USA. qchan2@email.uky.edu
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Chang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Beezhold
authors.forename: Vince
authors.initials: V
authors.lastname: Castranova
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D048055:Mitogen-Activated Protein Kinase 8
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