JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma

Chang Qingshan, Chen Jianguo, Beezhold, Castranova Vince, Shi Xianglin, Chen, Chen Fei

Description

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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 14
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

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Background due to hepatitis C viral (HCV) infection, alcohol abuse Hepatocellular carcinoma (HCC) has plagued popula- and non-alcoholic fatty liver disease [3-6]. HCC is the tions in Far East Asia, South Asia and Sub-Saharan Africa fourth most common neoplasm and the third most com- for several decades where the prevalence of hepatitis B mon cause of cancer-related death worldwide. Age- viral (HBV) infection and aflatoxin exposure is high[1,2]. adjusted HCC incidence rates vary from 2 per 100,000 A sharp increase in HCC incidence in North America, population in North America to 80 per 100,000 popula- Western Europe and Japan has been noted in recent years tion in China. Since most HCC patients are diagnosed

Bio Med Central

Research Open Access JNK1 activation predicts the pr ognostic outcome of the human hepatocellular carcinoma Qingshan Chang 1 , Jianguo Chen 3 , Kevin J Beezhold 2 , Vince Castranova 2 , Xianglin Shi 1,2 and Fei Chen* 2

Address: 1 Graduate Center for Toxico logy, University of Kentuc ky, Lexington, KY40536, USA, 2 Pathology and Physiology Research Branch, The Health Effects Laboratory Division, Nati onal Institute for Occupational Safety and Health, Morgantown, WV 26505, USA and 3 Qidong Liver Cancer Institute, Jiangsu Province, Qidong 226200, PR China Email: Qingshan Chang - [e-mail]; Jianguo Chen - [e-mail]; Kevin J Beezhold - [e-mail]; Vince Castranova - vcastranova@cdc. gov; Xianglin Shi - [e-mail] y.edu; Fei Chen* - [e-mail] * Corresponding author

Molecular Cancer

Published: 17 August 2009 Received: 19 April 2009 Molecular Cancer 2009, 8 :64 doi:10.1186/1476-4598-8-64  Accepted: 17 August 2009 This article is available from: http:/ /www.molecular-cancer.com/content/8/1/64 © 2009 Chang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with an extremely poor prognosis. The classification of HCC base d on the molecular signature is not well-established. Results: In the present study, we reported HCC si gnature genes based on the JNK1 activation status in 31 HCC specimens relative to the match ed 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 hepa toblastoma-type HCC. Many esta blished biomarkers for hepatic progenitor cells were over-expr essed in H-JNK1 HCC, includin g AFP, TACSTD1, KRT19, KRT7, THY1, and PROM1. In addition, the majority of th e most up-regulated gene s were those associated with metastasis and earlier re currence, whereas the genes fo r 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 stat us of JNK1 activation in HCC tissue, thus, might be a ne w biomarker for HCC prognosis and therapeutic targeting.