Differential gene expression in distinct virologic types of hepatocellular carcinoma: association with liver cirrhosis

Abstract

Using oligonucleotide microarray data of 45 hepatocellular carcinoma (HCC) samples, we evaluated gene expression in hepatitis B virus-positive and hepatitis C virus-positive HCCs (HBV-and HCV-HCCs) for an association with liver cirrhosis (LC). In all, 89 genes were expressed differentially between HBV-HCCs associated with LC and those not associated with LC. Among them, tumors from LC patients showed significantly lower expression levels of 72 genes and significantly higher levels of 17 genes than the levels found in tumors from non-LC patients. The former included genes responsible for signal transduction, transcription, metabolism, and cell growth. The latter included a tumor suppressor gene and a cell-growth-related gene. Only eight genes were expressed differentially between HCV-HCCs associated with and without LC. Our findings provide as a framework for clarifying the role of LC in HBV-and HCVrelated hepatocarcinogenesis.

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

“…HCC patients have various backgrounds and divergent clinical courses, resulting in much heterogeneity among tumor samples examined. 8,17 To address this heterogeneity among patients, we applied the Fisher ratio and the random permutation test to DNA microarray data. [7][8][9][10] Thus, the 46 genes selected as described above represent the molecular signature specific to IHR in a larger number of HCC cases.…”

“…5,[7][8][9][10] In our study, to search for genes related to early IHR, we used DNA microarray data from a sample of 33 HCCs, termed training sample, that was used to construct the predictor for early IHR (http://surgery2. med.yamaguchi-u.ac.jp/research/DNAchip/: released according to MIAME by Brazma et al…”

“…5,[7][8][9][10] Using a supervised learning method, we developed a DNA microarray-based system with only 12 genes for prediction of early IHR of HCC. 5 The 12-gene predictor detected accurately early IHR in HCC patients undergoing curative surgery; however, the 12 genes used are involved in a wide range of biological processes, and their roles in early IHR remain to be clarified.…”

“…[7][8][9][10] To decide how many genes we should consider, we used a random permutation test as described previously. [7][8][9][10] From the distribution of the Fisher ratios from randomized data, the top-ranking 46 genes with Fisher ratios >0.92 were considered to show statistically significant (p < 0.01) differences in expression between the 2 groups ( Fig. 1 and Table I).…”

Cell cycle regulation and hepatocarcinogenesis

“…Expression profiling of differentially expressed genes in human liver tumor samples using high density CDNA or oligonucleotide arrays has led to the identification of a large series of genes that are differentially regulated in vivo [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and also support the notion of multiple HCC phenotypes as discussed above. However, a major limitation of expression profiling performed thus far is that it provides only a snapshot of a single point in time and therefore could not distinguish those differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream, or secondary consequences.…”