Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma

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.

Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer

“…Of the dysregulated proteins linked to this pathway, 11 were upregulated and six were down-regulated. Collagen type I is transcribed from two separate genes, COL1A1 and COL1A2, both of which are methylated in association with decreased collagen expression in several human cancer cells (47,48), and bladder cancer tissues (49). Our data also showed that COL1A1, COL1A2, and COL18A1 proteins were down-regulated in bladder tumor cells compared with adjacent normal cells of bladder cancer patients.…”

Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric cancer

“…However, the expression levels of COL1A1 and COL1A2 in malignant tumors remain controversial. On one hand, frequent promoter methylation of COL1A1 was detected in renal cell carcinoma and hepatocellular carcinoma [9, 10], and COL1A2 was downregulated in melanoma [11], head and neck cancer [14], and bladder cancer [15]. On the other hand, COL1A1 and COL1A2 mRNA was upregulated in colorectal cancer and medulloblastoma [16, 17].…”

Proteomic Signatures of Thymomas

“…Existing studies have shown that COL1A1 (encoded by the collagen type 1 alpha 1 gene) has some predicative value in tumor diagnosis and prognosis where it has been found to be upregulated and downregulated in oral squamous cell carcinoma and hepatocellular carcinoma respectively. [25–27] Another explanation for the observed collagen changes is the reversion of the atrophied adult thymus composed mostly of adipocytes and stroma. However, few studies have been conducted on collagen composition changes in association with the thymus.…”