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Signature genes for both hepatoblastoma and hepatocellular carcinoma.
Chen-F; Li-S; Castranova-V
Eur J Gastroenterol Hepatol 2009 Oct; 21(10):1220-1222
A major goal in current hepatocellular carcinoma (HCC) research is to define molecular or gene signatures that govern initiation, maintenance and progression of the malignant tumours. The gene signature should be helpful in classifying tumour stages and predicting prognostic outcomes, such as metastasis, patient survival rate and recurrence of the tumours after resection. It is also highly desirable to use the gene signature to design targeted therapies or the so-called personalized medicine. Most recently, Cairo and colleagues reported signature genes for hepatoblastoma (HB), an infant liver tumour that is clinicopathologically distinctive from HCC. By comparing their data with our recent report on JNK1 activation and HCC gene profiling, a striking similarity between the genes in robust Cluster 2 (rC2) HB and the genes associated with the JNK1 activation status was noted. For the top 100 increased and bottom 100 decreased expressed genes in rC2 HB, 92 and 94% of these genes are presented among the most increased and decreased expressed genes in the HCC with higher JNK1 activation, respectively. Vice versa, 10 out of the 30 most upregulated genes and 20 out of the 30 most downregulated genes in the HCC with higher JNK1 activation are represented by the upregulated and downregulated genes in the HB or rC2 HB, respectively. A significant agreement of the 16 signature genes differentiating rC2 and rC1 HB (Fig. 6a of Cairo et al.) and the signature genes for the HCC with higher JNK1 activation was evident. The listed upregulated and downregulated genes in rC2 HB are fully overlapping with the upregulated and downregulated genes in HCC with higher JNK1 activity. In addition, as observed in rC2 HB, the liver progenitor markers AFP, TACSTD1, KRT19, KRT7 and imprinted genes are also substantially upregulated in the HCC with higher JNK1. Evidence to further support the similarity between rC2 HB and the HCC with higher JNK1 activation is the patient survival probability. The overall survival of both rC2 HB patients and HCC patients with higher JNK1 was substantially compromised. There are extensive debates on whether HCC arises exclusively from dedifferentiation of mature hepatocytes or maturation arrest of liver stem cells. As HB is a stem-like cell carcinoma, the similar gene signature in HB and HCC, thus, strengthens the notion that many HCCs are developed from liver stem cells and that the HB might be an early stage of HCC. In addition to HB and HCC, some of the liver progenitor markers are also overexpressed in intrahepatic cholangiocarcinoma.
Biological-factors; Biological-monitoring; Biomarkers; Cancer; Carcinogenesis; Carcinogenicity; Cell-function; Cell-metabolism; Cell-morphology; Cellular-function; Gastrointestinal-system; Gastrointestinal-system-disorders; Genes; Genetic-factors; Genotoxic-effects; Hepatocytes; Hepatotoxicity; Liver-cancer; Liver-disorders; Liver-microsomal-metabolism; Liver-microsomes; Liver-tumors; Tumors
Dr Fei Chen, PhD, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
Issue of Publication
European Journal of Gastroenterology and Hepatology
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division