Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling

Abstract

BACKGROUND The characterization of differentially expressed genes between cancerous and normal tissues is an important step in the understanding of tumorigenesis. Global gene expression profiling with microarrays has now offered a powerful tool to measure the changes of thousands of genes in any carcinoma tissues in an effort to identify these key disease‐related genes. To compare the gene expression of a primary liver carcinoma, metastatic carcinoma to the liver, and normal liver, the authors analyzed tissue from six primary hepatocellular carcinomas (HCCs), five colorectal adenocarcinoma metastases to the liver, and eight normal livers. METHODS Samples were processed from total RNA to fragmented cRNA and hybridized onto Affymetrix GeneChip® expression arrays. Analyses were performed to determine the consensus pattern of gene expression for primary liver carcinoma, metastatic liver carcinoma, and normal liver tissue and their changes in expression level. RESULTS In hepatocellular carcinoma, 842 genes were overexpressed, and 393 genes were underexpressed in comparison with genes of normal liver tissue. Of note, 7 of the 20 most increased identified known genes previously have been associated with liver carcinoma or other types of cancers. The 13 additional identified genes until now have not previously shown strong association with cancers. Furthermore, the authors identified 42 genes and 24 expressed sequence tags that are expressed at a significant level in both HCC and metastastic tumors, presenting a list of marker genes indicative of cancerous liver tissue. CONCLUSIONS In this study, genes that can be involved in the production of and maintenance of hepatic carcinomas were identified. These data offer new insight into genes that are potentially important in the pathogenesis of liver carcinoma, as well as additional targets for new strategies for cancer therapy and treatment. Cancer 2001;92:395–405. © 2001 American Cancer Society.

Platelet-derived growth factor receptor-α: a novel therapeutic target in human hepatocellular cancer

“…Although some reports have examined the expression patterns of multiple genes in these tumors, these studies are limited by reproducibility and ability to address 'cause or effect' relationship of observed changes (28,29). Although inclusion of controls and tumors at various stages of progression might assist in addressing the latter issue to an extent, the interpretation might be complicated by heterogeneity in the tumors or patient population.…”

Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents

“…This classification can lead to improved predications of patient outcome (1)(2)(3)(4) and possibly predict sensitivity to anticancer agents (5). A comparison of gene expression profiles between primary tumors and metastases has also identified genes that may be involved in the etiology of metastasis (6,7), and a comparison between normal and malignant tissues can identify possible diagnostic markers of cancer as well as potential therapeutic targets (8,9).…”

Hepatocellular carcinoma

“…The HBV-encoded "e" antigen (HBeAg) is also associated with HCC development (30), although most carriers with HCC are anti-HBe positive years before tumor diagnosis. Other reports, with microarray analysis, show altered expression of host gene products in tumor compared with nontumor (31)(32)(33)(34), but it is not clear whether these changes reflect early or late events in hepatocarcinogenesis, or whether any will be useful as diagnostic or prognostic markers of HCC. Recently, antibodies in HCC sera, binding to a subset of proteins in a cDNA expression library, suggest that changes in gene expression in tumor compared with normal liver could trigger antibody responses that might identify tumor-bearing patients (35).…”