透過您的圖書館登入
IP:3.144.252.140
  • 學位論文

肝硬化相關細胞激素對B型肝炎誘導肝細胞癌之預測:蛋白質微陣列分析

Identification of Cytokines Involved in HBV-Related Cirrhosis for Hepatocellular Carcinoma Prediction: A Protein Microarray Analysis

指導教授 : 于明暉
共同指導教授 : 莊曜宇

摘要


無資料

並列摘要


Background Early identification of high risk population for liver cirrhosis may be beneficial to hepatitis B virus (HBV) carriers and their prognosis on hepatocellular carcinoma (HCC). We aimed to identify differently expressed cytokines in plasma between clinical liver cirrhosis patients and asymptomatic HBV carriers as biomarkers for HCC prediction. Methods A total of 174 cytokines were assessed in plasma from 16 HBsAg carriers at different stages of liver cirrhosis using cytokine antibody microarrays. Ten promising cytokines were later evaluated in a case-control study including 49 HCC cases and 50 matched controls nested within a longitudinal cohort study of HBsAg carriers by using quantitative antibody arrays. Blood samples from each study subject were collected up to 16 years before diagnosis of HCC. Results Forty-five cytokines were differentially expressed among asymptomatic carriers, Child-Pugh stage A patients and Child-Pugh stage B/C patients (parametric P-value range: 0.0006-0.0487, empirical P-value range: 0.0003-0.0556, false-discovery rate q-value range=0.0713-0.1244). Evaluation of a subset of 10 cytokines, including ICAM-2, MCP-1, EGF, CXCL-16, IGFBP-2, sTNFRII, TIMP4, Fas, RANTES, and TIMP-1, by a nested case-control study showed that only plasma ICAM-2 levels were significantly different between HCC cases and controls at baseline (P-value for Wilcoxon sum rank test = 0.0413). Plasma ICAM-2 levels exhibited an accuracy (AUC=0.6208) comparable to HBV viral load (AUC=0.6022) and superior to serum ALT (AUC=0.5965) for prediction of HCC. Conclusion Results of this study suggested that ICAM-2 may serve as a promising noninvasive biomarker for prediction of HCC development. Key Words Cytokines, Hepatitis B, liver cirrhosis, hepatocellular carcinoma, microarrays

參考文獻


1. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529-38.
2. Stevens CE, Beasley RP, Tsui J, Lee WC. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975;292:771-4.
3. Chen CJ, Wang LY, Yu MW. Epidemiology of hepatitis B virus infection in the Asia-Pacific region. J Gastroenterol Hepatol 2000;15 Suppl:E3-6.
4. Chen DS. From hepatitis to hepatoma: lessons from type B viral hepatitis. Science 1993;262:369-70.
5. Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ. Viral hepatocarcinogenesis: from infection to cancer. Liver Int 2008;28:175-88.

延伸閱讀