Differential Proteomic Analysis of Hepatocellular Carcinomas from Knockout Mice and Normal (Knockout) Livers.
(2020) Cancer Genomics & Proteomics — Vol. 17, n° 6, p. 669-685 (2020)
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- BACKGROUND: Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Mice lacking the tumor-suppressive protein phosphatase 2A subunit B56δ (Ppp2r5d) spontaneously develop HCC, correlating with increased c-MYC oncogenicity. MATERIALS AND METHODS: We used two-dimensional difference gel electrophoresis-coupled matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to identify differential proteomes of livers from wild-type, non-cancerous and HCC-affected B56δ knockout mice. RESULTS: A total of 23 proteins were differentially expressed/regulated in liver between wild-type and non-cancerous knockout mice, and 119 between non-cancerous and HCC knockout mice ('cancer proteins'). Overlap with our reported differential transcriptome data was poor. Overall, 56% of cancer proteins were reported before in HCC proteomics studies; 44% were novel. Gene Ontology analysis revealed cancer proteins mainly associated with liver metabolism (18%) and mitochondria (15%). Ingenuity Pathway Analysis identified 'cancer' and 'gastrointestinal disease' as top hits. CONCLUSION: We identified several proteins for further exploration as novel potential HCC biomarkers, and independently underscored the relevance of Ppp2r5d knockout mice as a valuable hepatocarcinogenesis model.
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Lambrecht, C., Ferreira, G. B., Omella, J. D., Libbrecht, L., De Vos, R., Derua, R., Mathieu, C., Overbergh, L., Waelkens, E., & Janssens, V. (2020). Differential Proteomic Analysis of Hepatocellular Carcinomas from Knockout Mice and Normal (Knockout) Livers. Cancer Genomics & Proteomics, 17(6), 669-685. https://doi.org/10.21873/cgp.20222 (Original work published 2020)