Proteome Differences between Hepatitis B Virus Genotype-B- and Genotype-C-Induced Hepatocellular Carcinoma Revealed by iTRAQ-Based Quantitative Proteomics

Hepatitis
B virus (HBV) is the main cause of hepatocellular carcinoma
(HCC) in southeast Asia where HBV genotype B and genotype C are the
most prevalent. Viral genotypes have been reported to significantly
affect the clinical outcomes of HCC. However, the underlying molecular
differences among different genotypes of HBV virus infected HCC have
not been revealed. Here, we applied isobaric tags for relative and
absolute quantitation (iTRAQ) technology integrated with liquid chromatography–tandem
mass spectrometry (LC–MS/MS) analysis to identify the proteome
differences between the HBV genotypes B- and C-induced HCC. In brief,
a total of 83 proteins in the surrounding noncancerous tissues and
136 proteins in the cancerous tissues between HBV genotype-B- and
genotype-C-induced HCC were identified, respectively. This information
revealed that there might be different molecular mechanisms of the
tumorigenesis and development of HBV genotypes B- and C-induced HCC.
Furthermore, our results indicate that the two proteins ARFIP2 and
ANXA1 might be potential biomarkers for distinguishing the HBV genotypes
B- and C-induced HCC. Thus, the quantitative proteomic analysis revealed
molecular differences between the HBV genotypes B- and C-induced HCC,
and might provide fundamental information for further deep study.

乙型肝炎病毒（Hepatitis B virus, HBV）是东南亚地区肝细胞癌（hepatocellular carcinoma, HCC）的主要致病诱因，该区域以HBV基因型B与基因型C为流行优势毒株。已有研究证实，病毒基因型可显著影响肝细胞癌的临床预后，但HBV不同基因型感染所致肝细胞癌之间的潜在分子差异尚未被阐明。本研究采用同位素相对与绝对定量标签技术（isobaric tags for relative and absolute quantitation, iTRAQ）联合液相色谱-串联质谱（liquid chromatography–tandem mass spectrometry, LC-MS/MS）分析，以鉴定HBV基因型B、C诱导的肝细胞癌之间的蛋白质组差异。简言之，针对HBV基因型B与基因型C诱导的肝细胞癌，本研究分别在其癌旁非癌组织与癌组织中鉴定出83种与136种差异蛋白。上述结果表明，HBV基因型B与C诱导的肝细胞癌在肿瘤发生与发展进程中可能存在迥异的分子机制。此外，本研究结果显示ARFIP2与ANXA1这两种蛋白或可作为区分两类HBV基因型诱导肝细胞癌的潜在生物标志物。综上，本定量蛋白质组学分析揭示了HBV基因型B、C诱导的肝细胞癌之间的分子差异，可为后续深入研究提供基础性依据。