Abstract
Integrins are a large family of cell surface receptors that bind extracellular matrix proteins and participate in cancer progression. However, the prognostic value of integrin family genes in post-operative patients with HBV-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated 18 single nucleotide polymorphisms (SNPs) in integrin family genes and found that the AG/GG genotypes at rs988574 in ITGA1 predicted a better prognosis compared to carriers of the AA genotype (P = 0.025, HR = 0.69, 95%CI = 0.50–0.96). Moreover, rs988574 genotype combined with serum level of AFP had a better prognostic value in HBV-related HCC patients (P = 0.026, HR = 1.75, 95% CI = 1.07–2.85). Furthermore, we compared the expression of 24 integrin family genes in HBV-related HCC tissues and adjacent normal tissues. Survival analysis demonstrated that expression of three of the family members, ITGA5, ITGB5 and ITGA2B, were significantly associated with the overall survival (OS) or relapse-free survival (RFS) of HBV-related HCC patients. Additionally, patients with lower expression of both ITGA5 and ITGB5 had the best OS and RFS (P = 0.017 and P = 0.002, respectively). Our study demonstrated that rs988574 of ITGA1 and the expression of ITGA5, ITGB5 and ITGA2B are potential independent prognostic bio-markers and therapeutic targets for HBV-related HCC patients and may be useful for the diagnosis of HBV-related HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide [1]
We investigated 18 single nucleotide polymorphisms (SNPs) in integrin family genes and found that the AG/GG genotypes at rs988574 in ITGA1 predicted a better prognosis compared to carriers of the AA genotype (P = 0.025, hazard ratios (HR) = 0.69, 95%95% confidence interval (CI) = 0.50–0.96)
In a multivariate Cox proportional hazards ratio analysis adjusting for age, gender, cirrhosis, Barcelona Clinic Liver Cancer (BCLC) stage and serum alpha fetoprotein (AFP) levels, we found that among the 24 integrin family genes, ITGA5, ITGB5 and ITGA2B were significantly associated with prognosis in terms of overall survival (OS) or relapse-free survival (RFS) of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (Tables 5 and 6; P < 0.05)
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide [1]. Integrins are involved in a wide range of biological activities and pathological processes, especially carcinogenesis and cancer progression [16, 17]. They regulate cell–cell and cell–ECM interactions, and this ‘outside-in’ signaling activates a number of signaling pathways that are important in the regulation of cell shape, survival, gene transcription and migration [18, 19]. We evaluated the prognostic predictive value of integrin family genes and ITGA1 single nucleotide polymorphism (SNP) rs988574 in HBVrelated HCC patients by performing prognostic analysis in 221 newly diagnosed pathologically confirmed HBVrelated HCC patients. We found that patients carrying the AG or GG genotypes at rs988574 had better prognosis than those with the AA genotype
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