tailieunhanh - Báo cáo khoa học: Proteomic mining in the dysplastic liver of WHV⁄c-myc mice – insights and indicators for early hepatocarcinogenesis

Because of the asymptomatic process of carcinogenesis, the early detection of cancers such as hepatocellular carcinoma (HCC) is very challenging. Tumor-prone transgenic mouse models of oncogenesis can provide a stable and powerful tool for the analysis of cancer initiation, and are therefore promising for the discovery of early putative biomarkers of HCC. | Proteomic mining in the dysplastic liver of WHV c-myc mice - insights and indicators for early hepatocarcinogenesis Yansheng Liu1 Chen Li1 Zhen Xing2 Xingyu Yuan1 Yi Wu1 Mengjie Xu1 Kang Tu1 Qingrun Li1 Chaochao Wu1 Mujun Zhao2 and Rong Zeng1 1 Key Laboratory of Systems Biology Institute of Biochemistry and CellBiology Shanghai Institutes for BiologicalScience Chinese Academy of Sciences China 2 Institute of Biochemistry and CellBiology Shanghai Institutes for BiologicalSciences Chinese Academy of Sciences China Keywords c-Myc early biomarker hepatocellular carcinoma mouse model MS Correspondence R. Zeng and M. Zhao 320 YueYang Road Shanghai 200031 China Fax 86 21 54920171 Tel 86 21 54920170 E-mail zr@ mjzhao@ These authors contributed equally to this work Received 20 April2010 revised 21 June 2010 accepted 28 July 2010 doi Because of the asymptomatic process of carcinogenesis the early detection of cancers such as hepatocellular carcinoma HCC is very challenging. Tumor-prone transgenic mouse models of oncogenesis can provide a stable and powerful tool for the analysis of cancer initiation and are therefore promising for the discovery of early putative biomarkers of HCC. Using a label-free proteomic quantification strategy we comprehensively investigated the protein expression profile in the livers of three 2-month-old WHV c-myc mice at the dysplastic stage with age-matched wt-C57 mice as controls. We identified 2781 proteins 540 of which were differentially expressed. These proteins successfully characterized certain precancerous biological processes and alterations in transcriptional regulators before tumor onset. Two candidates FK506-binding protein 4 FKBP52 and ferritin heavy chain were taken as examples for a search from the mouse model to clinical human tissues. Their levels in serum samples were determined by western blotting and showed a noteworthy ability to distinguish between HCC and control cases. .