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Prognostic value of integrin variants and expression in post-operative patients with HBV-related hepatocellular carcinoma.

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.

SUBMITTER: Shang L

PROVIDER: S-EPMC5652745 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Prognostic value of integrin variants and expression in post-operative patients with HBV-related hepatocellular carcinoma.

Shang Liming L Ye Xinping X Zhu Guangzhi G Su Hao H Su Zhixiong Z Chen Bin B Xiao Kaiyin K Li Lequn L Peng Minhao M Peng Tao T

Oncotarget 20170810 44

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 <i>ITGA1</i> predicted a better prognosis compared to carriers of the A ...[more]

PMID: 29100351

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Project description:Background: Hepatocellular carcinoma (HCC) is a main cause of malignancy-related death all over the world with a poor prognosis. The current research is focused on developing novel prognostic and diagnostic models of Hepatocellular carcinoma from the perspective of hepatitis B virus (HBV)-related genes, and predicting its prognostic characteristics and potential reliable biomarkers for Hepatocellular carcinoma diagnosis. Methods: As per the information related to Hepatocellular carcinoma expression profile and the clinical data in multiple public databases, we utilized limma for assessing the differentially expressed genes (DEGs) in HBV vs non- hepatitis B virus groups, and the gene set was enriched, analyzed and annotated by WebGestaltR package. Then, STRING was employed to investigate the protein interactions. A risk model for evaluating Hepatocellular carcinoma prognosis was built with Lasso Cox regression analysis. The effect patients receiving immunotherapy was predicted using Tumor Immune Dysfunction and Exclusion (TIDE). Additionally, pRRophetic was used to investigate the drug sensitivity. Lastly, the Support Vector Machine (SVM) approach was utilized for building the diagnostic model. Results: The Hepatocellular Carcinoma Molecular Atlas 18 (HCCDB18) data set was utilized for the identification of 1344 HBV-related differentially expressed genes, mainly associated with cell division activities. Five functional modules were established and then we built a prognostic model in accordance with the protein-protein interaction (PPI) network. Five HBV-related genes affecting prognosis were identified for constructing a prognostic model. Then, the samples were assigned into RS-high and -low groups as per their relevant prognostic risk score (RS). High-risk group showed worse prognosis, higher mutation rate of TP53, lower sensitivity to immunotherapy but higher response to chemotherapeutic drugs than low-risk group. Finally, the hepatitis B virus diagnostic model of Hepatocellular carcinoma was established. Conclusion: In conclusion, the prognostic and diagnostic models of hepatitis B virus gene-related Hepatocellular carcinoma were constructed. ABCB6, IPO7, TIMM9, FZD7, and ACAT1, the five HBV-related genes that affect the prognosis, can work as reliable biomarkers for the diagnosis of Hepatocellular carcinoma, giving a new insight for improving the prognosis, diagnosis, and treatment outcomes of HBV-type Hepatocellular carcinoma.

Dataset Information

Prognostic value of integrin variants and expression in post-operative patients with HBV-related hepatocellular carcinoma.

Publications

Prognostic value of integrin variants and expression in post-operative patients with HBV-related hepatocellular carcinoma.

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