Differentially Expressed Genes between Early and Advanced Hepatocellular Carcinoma (HCC) as a Potential Tool for Selecting Liver Transplant Recipients

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Liver transplantation (LT) represents a curative treatment for "small" HCC. Preoperative staging is critical in selecting optimal candidates for LT to optimize the use of this scarce resource. From December 1997 to February 2004, 148 patients diagnosed with cirrhosis and HCC were evaluated at our center. After staging, the patients were listed for LT according to United Network for Organ Sharing (UNOS) criteria. When pretransplant liver MRIs were compared with the findings of the explanted livers, 8 of 35 patients (22.8%) were understaged. Three of the 8 patients (37.5%) had recurrence post-LT. A retrospective gene expression profiling study was done using microarray technology for tumor samples in the pretransplant hepatitis C virus (HCV)-HCC understaged patients and in a contemporaneous group of HCV-HCC patients that were accurately staged. Two sample t tests comparing the early versus advanced HCV-HCCs with respect to gene expression showed an important set of genes differentially expressed among the samples. Hierarchical clustering analysis of the gene expression profiling classified 93.8% of the total tumor samples and 85.7% of the understaged samples in concordance with the explanted pathological staging. We found a distinctive pattern of gene expression between early and advanced HCV-HCCs. These results suggest that gene expression profiling could improve the pre-LT HCC staging to more closely mimic the explant pathology. Whether gene expression profiling of HCC will be refined to the point of predicting potential metastatic biologic behavior to predict post-LT recurrence will require longitudinal prospective study of this gene array technology.

Fatal ischemic acute pancreatitis complicating trans-catheter arterial embolization of small hepatocellular carcinoma: Do the risks outweigh the benefits?

“…However, there is an urgent need to identify strong predictors of progression while patients are on the waiting list. Ongoing genomic and proteomic studies will characterize HCC more accurately, so that, in the future, HCC patients may be classified and treated according to their molecular profile and not according to the rough evaluation of tumour burden and conventional measures of liver function [23].…”

Functional and Topological Properties in Hepatocellular Carcinoma Transcriptome

“…These datasets corresponded to 264 arrays [44], [66], [67]. In the HCC Dataset, ‘Normal Liver’ refers to 5 pools of non-tumorous liver tissue, specifically alcoholic cirrhosis, alcoholic noncirrhotic liver, HBV noncirrhotic liver, HCV cirrhosis, and HBV cirrhosis.…”

High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma

“…As in other disease areas, through use of high-throughput technologies, a vast amount of information is being accumulated for the study of hepatocellular carcinoma (HCC). To date, most high-throughput genomic research in HCC has emphasized gene expression levels (Iizuka et al 2004; Mas et al 2006; Nam et al 2005). However, the importance of epigenetic events is being elucidated, as aberrant methylation has been reported to lead to chromosomal instability (Baylin et al 2000, 2001).…”