Proteomics analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi,China / 中华肝胆外科杂志

ABSTRACT

Objective To explore the effects and the molecular mechanism of synergistic hepatocarcinogenesis of HBV and AFB1 in the development of HCC by studying the difference in protein expression profiles in hepatocellular carcinoma exposed to hepatitis B virus and Aflatoxin B1.Method 32 HCC specimens were labeled under four categories based on their biomarkers of HBV and AFB1 exposuregroup AHBV(+)/AFB1 (+),10 cases,group BHBV(+)/AFB1 (-),10 cases,group CHBV(-)/AFB1(+),6 cases,groupDHBV(-)/AFB1(-),6 cases.Normal hepatic tissues from 10 cases of hepatic hemangioma,liver resection and liver transplant donor were chosen as the normal control group.Isobaric Tagging Reagent Quantitative (iTRAQ) Proteomics together with 2DLC MS/MS were applied to analyze the differentially expressed proteins among the 4 groups.Result (1) A total of 117 unique differentially expressed proteins including 53 up-regulated proteins and 64 down-regulated proteins were identified in the four groups.The number of unique differentially expressed proteins,including up-regulated and down-regulated proteins,in group A,group B,group C and group D were 106,97,104 and 74 respectively.(2) Among the 117 differentially expressed proteins,9 proteins were heat shock proteins or chaperones,and they were up regulated in group A,B and C.Besides,15 proteins were detoxification and drug metabolism pathway related proteins,12 of them were down-regulated in group A,and more than half of them were also down-regulated in group B and C.(3) The Reverse Transcriptase PCR result showed the mean expression level of AKR1B10 mRNA in group A was significantly higher than group B,C and D (all P＜0.05,respectively).Group C also showed significantly a higher expression level of AKR1B10 mRNA than group D (P＜0.05).The Western-blot results showed the mean expression level of AKR1B10 protein in group A was significantly higher than group B and D (all P＜0.05,respectively).Conclusions The up-regulated expression of heat shock protein and the down-regulated expression of most protein enzymes related to detoxification and drug metabolism were the common molecular biological events of HCC associated with exposure to HBV and AFB1.This suggested the synergistic hepatocarcinogenesis effects of HBV and AFB1 may be related to dysregulation of protein enzymes related to detoxification and drug metabolism.The overexpression of AKR1B10 may be involved in the AFB1-related hepatocarcinogenesis process.