title: Serpin peptidase inhibitor (SERPINB5) haplotypes are associated with susceptibility to hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. The serpin peptidase inhibitor SERPINB5 is a tumour-suppressor gene that promotes the development of various cancers in humans. However, whether SERPINB5 gene variants play a role in HCC susceptibility remains unknown. In this study, we genotyped 6 SNPs of the SERPINB5 gene in an independent cohort from a replicate population comprising 302 cases and 590 controls. Additionally, patients who had at least one rs2289520 C allele in SERPINB5 tended to exhibit better liver function than patients with genotype GG (Child-Pugh grade A vs. B or C; P = 0.047). Next, haplotype blocks were reconstructed according to the linkage disequilibrium structure of the SERPINB5 gene. A haplotype "C-C-C" (rs17071138 + rs3744941 + rs8089204) in SERPINB5-correlated promoter showed a significant association with an increased HCC risk (AOR = 1.450; P = 0.031). Haplotypes "T-C-A" and "C-C-C" (rs2289519 + rs2289520 + rs1455555) located in the SERPINB5 coding region had a decreased (AOR = 0.744; P = 0.031) and increased (AOR = 1.981; P = 0.001) HCC risk, respectively. Finally, an additional integrated in silico analysis confirmed that these SNPs affected SERPINB5 expression and protein stability, which significantly correlated with tumour expression and subsequently with tumour development and aggressiveness. Taken together, our findings regarding these biomarkers provide a prediction model for risk assessment.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chao-Bin
authors.initials: CB
authors.lastname: Yeh
authors.affiliation: Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ying-Erh
authors.initials: YE
authors.lastname: Chou
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan.|Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
mesh_terms: D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015843:Serpins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C085344:SERPIN-B5; D015843:Serpins