JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma

Qingshan Chang, Jianguo Chen, Kevin J. Beezhold, Vince Castranova, Xianglin Shi, Fei Chen

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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. Conclusion: 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.

Original languageEnglish
Article number64
JournalMolecular Cancer
Volume8
DOIs
StatePublished - Aug 17 2009

Bibliographical note

Funding Information:
We thank Dr. Xin Wei Wang, at the Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, NCI/NIH (Bethesda, MD), for sharing his unpublished cDNA array data with us for comparison. We also thank the members in the Biostatistics and Epidemiology Branch of NIOSH for the renormalization of the gene profiling data. This research project was partially supported through NIOSH/CDC intramural funding (9270036) to F.C.

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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