cDNA Microarray Analysis of Macroregenerative and Dysplastic Nodules in End-Stage Hepatitis C Virus-Induced Cirrhosis

Abstract

Hepatocellular carcinoma is a common malignancy causing significant morbidity and mortality worldwide. In this study we use expression microarray technology to identify novel genes that consistently displayed altered expression levels in the earliest identifiable precursors to hepatocellular carcinoma, dysplastic and macroregenerative nodules. The gene expression profiles from nine patients with end-stage hepatitis C cirrhosis that contained a combined 11 dysplastic or macroregenerative nodules were compared to the patient's matched cirrhotic liver tissue. A total of 53 genes were consistently dysregulated in the patient liver specimens. Six of seven genes were validated by quantitative real-time reverse transcriptase-polymerase chain reaction, or by immunohistochemical studies performed on an independent set of lesions. The novel genes, including caveolin-1, semaphorin E, and FMS-like tyrosine kinase 3 ligand, have putative roles in carcinogenesis but have not been reported in hepatocellular carcinogenesis. Microarray expression analysis of dysplastic and macroregenerative liver nodules provide insight into the earliest changes in hepatocellular carcinogenesis.

IκB Kinase α-Mediated Derepression of SMRT Potentiates Acetylation of RelA/p65 by p300

“…Reactions were subjected to the following amplification conditions: 95°C for 900 s followed by 40 cycles of 95°C for 15 s and 60°C for 60 s using the 7500 Real-Time PCR system (PE Biosciences). The degree of change in transcripts was calculated as described previously (3). Briefly, we divided the ratio of the normalized copies of the experimental gene in dimethyl sulfoxide (DMSO) by the normalized copies of the experimental gene in Bay 11.…”

Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions

“…[20][21][22][23] However, mRNA expression analysis is hampered, since in livers bearing hepatocellular carcinoma the non-neoplastic tissues already reveal distinct dysregulated sets of genes as also found in hepatocellular carcinoma. [24][25][26] We therefore focused on the comparison of hepatocellular carcinoma and hepatocellular adenoma, a rare tumour, almost never reported as becoming malignant.…”

“…This qualifies hepatocellular adenoma as a comparison group since the surrounding tissue in livers harbouring hepatocellular carcinoma often contains significant alterations in gene expression and on the genomic level similar to those found in hepatocellular carcinoma. [13][14][15] During dedifferentiation of hepatocellular carcinoma, chromosomal instability increases from differentiated G1 to undifferentiated G3 tumours. Recurrent chromosome aberrations of hepatocellular carcinoma are gains of 1q, 8q, 6q, and 20q and losses of 4q, 8p, 13q, and 17p.…”

Microarray-based analysis for hepatocellular carcinoma: From gene expression profiling to new challenges

“…After chronic infection forces hepatocytes to regenerate with consequently excessive replication, regenerative nodules appear as precancerous lesions. Genes responsible for hepatocarcinogenesis may be identified through comparison of expression profiles between regenerative nodules and early liver cancer [55][56][57] . On the other hand, we and other groups have highlighted HCC with nodule-innodule appearance to investigate gene alterations in the course of liver cancer progression [58,59] .…”