Identification of the collagen type 1 alpha 1 gene COL1A1 as a candidate survival-related factor associated with hepatocellular carcinomaReport as inadecuate




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BMC Cancer

, 14:108

Translational oncology

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.

KeywordsHepatocellular carcinoma Collagen type 1 alpha 1 Methylation AbbreviationscDNAComplementary DNA

COL1A1Collagen type 1 alpha 1

ECMextracellular matrix

HCCHepatocellular carcinoma

HDGFhepatoma-derived growth factor

LOHLoss of heterozygosity

MSPMethylation-specific PCR

PCRPolymerase chain reaction

RFARadiofrequency ablation

SNPSingle nucleotide polymorphism

TAETransarterial chemoembolization

UMSPUnmethylation-specific PCR.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-108 contains supplementary material, which is available to authorized users.

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Author: Masamichi Hayashi - Shuji Nomoto - Mitsuhiro Hishida - Yoshikuni Inokawa - Mitsuro Kanda - Yukiyasu Okamura - Yoko Nishikaw

Source: https://link.springer.com/







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