An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer deaths worldwide. New diagnostic and therapeutic options are needed for more effective and early detection and treatment of this malignancy. We identified 703 genes that are highly expressed in HCC using DNA microarrays, and further characterized them in order to uncover novel tumor markers, oncogenes, and therapeutic targets for HCC. Using Gene Ontology annotations, genes with functions related to cell proliferation and cell cycle, chromatin, repair, and transcription were found to be significantly enriched in this list of highly expressed genes. We also identified a set of genes that encode secreted (e.g. GPC3, LCN2, and DKK1) or membrane-bound proteins (e.g. GPC3, IGSF1, and PSK-1), which may be attractive candidates for the diagnosis of HCC. A significant enrichment of genes highly expressed in HCC was found on chromosomes 1q, 6p, 8q, and 20q, and we also identified chromosomal clusters of genes highly expressed in HCC. The microarray analyses were validated by RT-PCR and PCR. This approach of integrating other biological information with gene expression in the analysis helps select aberrantly expressed genes in HCC that may be further studied for their diagnostic or therapeutic utility.

Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

“…6,10,12 Unexpectedly, a relatively small number of genes (4 out of 42) fell into these two groups in our work. This may be explained by the use of relatively stringent criteria for selecting the candidate genes in the current study.…”

“…These processes were reported previously to be involved mainly in various pathological injuries to the liver, or the development of HCC. [9][10][11][12] Among these identified genes, several have been reported as important hepatocarcinogenic factors. Apolipoprotein B (apo-B) mRNA-editing enzyme catalytic polypeptide 1 (Apobec-1), a cytidine deaminase catalytic subunit of the multiprotein editing complex, has been shown to be upregulated in HBx transgenic livers and HCC tissues (Fig.…”

Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development

“…In line with this assumption, enhanced levels of ANXA1 were detected in lung and oral SCCs (Leethanakul et al, 2000;Petroziello et al, 2004) and LCN2 was highly expressed in hepatocellular carcinomas (Patil et al, 2005). Moreover, recent analysis of cancer-related genes with increased mRNA abundance in common human malignancies revealed significant transcriptional activation on human chromosome 1q21, also known as epidermal differentiation cluster (Glinsky et al, 2003a, b).…”

Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma

“…In contrast, expression of GPC3 mRNA was markedly increased in 20 of 30 HCC samples, and was moderately increased in five of 30 HCC samples [27]. In a genomics study, investigators used cDNA microarrays containing 17,000 unique human genes to study the gene expression profiles in over 200 liver tissue samples, including 102 primary HCC (from 82 patients) and 74 nontumor liver tissues [28]. GPC3 showed the highest magnitude increase for the 'Membrane protein' category, and was second only to alpha-fetoprotein (AFP) in the 'Secretory or extracellular proteins' category.…”