Abstract
BackgroundADAMTS14 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which are proteolytic enzymes with a variety of further ancillary domain in the C-terminal region for substrate specificity and enzyme localization via extracellular matrix association. However, whether ADAMTS14 genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown.Methodology/Principal findingsFour non-synonymous single-nucleotide polymorphisms (nsSNPs) of the ADAMTS14 gene were examined from 680 controls and 340 patients with HCC. Among 141 HCC patients with smoking behaviour, we found significant associations of the rs12774070 (CC+AA vs CC) and rs61573157 (CT+TT vs CC) variants with a clinical stage of HCC (OR: 2.500 and 2.767; 95% CI: 1.148–5.446 and 1.096–6.483; P = 0.019 and 0.026, respectively) and tumour size (OR: 2.387 and 2.659; 95% CI: 1.098–5.188 and 1.055–6.704; P = 0.026 and 0.034, respectively), but not with lymph node metastasis or other clinical statuses. Moreover, an additional integrated in silico analysis proposed that rs12774070 and rs61573157 affected essential post-translation O-glycosylation site within the 3rd thrombospondin type 1 repeat and a novel proline-rich region embedded within the C-terminal extension, respectively.ConclusionsTaken together, our results suggest an involvement of ADAMTS14 SNP rs12774070 and rs61573157 in the liver tumorigenesis and implicate the ADAMTS14 gene polymorphism as a predict factor during the progression of HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies of the liver and represents the second and sixth leading cause of cancer related death among males and females in 2012, respectively [1]
Our results suggest an involvement of ADAMTS14 SNP rs12774070 and rs61573157 in the liver tumorigenesis and implicate the ADAMTS14 gene polymorphism as a predict factor during the progression of HCC
The incidence of HCC shows that genetic mutations and environmental factors may increase the severity of the hepatic inflammation that lead to cell differentiation, proliferation and the deposition of connective tissue, which are necessary for the pathophysiology of hepatocarcinogenesis [4,5,6]
Summary
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies of the liver and represents the second and sixth leading cause of cancer related death among males and females in 2012, respectively [1]. ADAMTS14 [7,8,9], which is located on chromosome 10q22.1, belongs to the ADAMTS ( known as a disintegrin and metalloproteinase domain with thrombospondin motifs) zinc ion-dependent proteinase family [10, 11] that contains an N-terminal catalytic domain and a C-terminal ancillary domain which defines substrate specificity including thrombospondin type 1 repeats (TSR) domain [12] and an unique proline-rich region (PRR) [13, 14] that was found to be essential for recognition of its procollagen substrates. ADAMTS14 is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs), which are proteolytic enzymes with a variety of further ancillary domain in the C-terminal region for substrate specificity and enzyme localization via extracellular matrix association. Whether ADAMTS14 genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown
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