Research

JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma

Qingshan Chang¹ , Jianguo Chen³ , Kevin J Beezhold² , Vince Castranova² , Xianglin Shi^1,2 and Fei Chen²

¹  Graduate Center for Toxicology, University of Kentucky, Lexington, KY40536, USA

²  Pathology and Physiology Research Branch, The Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

³  Qidong Liver Cancer Institute, Jiangsu Province, Qidong 226200, PR China

author email corresponding author email

Molecular Cancer 2009, 8:64doi:10.1186/1476-4598-8-64

Published:	17 August 2009

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.