Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations. It is urgent that we identify carcinogenesis-related genes to establish an innovative treatment strategy for this disease.MethodsTriple-combination array analysis was performed using one pair each of HCC and noncancerous liver samples from a 68-year-old woman. This analysis consists of expression array, single nucleotide polymorphism array and methylation array. The gene encoding collagen type 1 alpha 1 (COL1A1) was identified and verified using HCC cell lines and 48 tissues from patients with primary HCC.ResultsExpression array revealed that COL1A1 gene expression was markedly decreased in tumor tissues (log2 ratio –1.1). The single nucleotide polymorphism array showed no chromosomal deletion in the locus of COL1A1. Importantly, the methylation value in the tumor tissue was higher (0.557) than that of the adjacent liver tissue (0.008). We verified that expression of this gene was suppressed by promoter methylation. Reactivation of COL1A1 expression by 5-aza-2′-deoxycytidine treatment was seen in HCC cell lines, and sequence analysis identified methylated CpG sites in the COL1A1 promoter region. Among 48 pairs of surgical specimens, 13 (27.1%) showed decreased COL1A1 mRNA expression in tumor sites. Among these 13 cases, 10 had promoter methylation at the tumor site. The log-rank test indicated that mRNA down-regulated tumors were significantly correlated with a poor overall survival rate (P = 0.013).ConclusionsTriple-combination array analysis successfully identified COL1A1 as a candidate survival-related gene in HCCs. Epigenetic down-regulation of COL1A1 mRNA expression might have a role as a prognostic biomarker of HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations
Because no study had revealed the correlation of collagen type 1 alpha 1 (COL1A1) with HCC, we aimed to evaluate the relevance of COL1A1 expression in HCC samples
Triple-combination array We first searched for candidate tumor suppressor genes by expression array analysis, focusing on genes with more decreased expression levels in HCC tissue than adjacent noncancerous tissue
Summary
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations. It is urgent that we identify carcinogenesis-related genes to establish an innovative treatment strategy for this disease. Hepatocellular carcinoma (HCC) is diagnosed in more than half a million people worldwide [2]. Liver resection is the treatment of choice for HCC. We have some options for postoperative treatment, including local radiofrequency ablation (RFA), transarterial chemoembolization (TAE), radioembolization, and molecular targeted therapy. Establishment of more precise prognostic determinants using molecular biology techniques is warranted to make the best use of these options. Surgical samples and matched clinical data were used to identify a prognostic marker, focusing on the genomic alterations of hepatic carcinogenesis
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