Giuliana Cavalloni1, Caterina Peraldo-Neia2, Annamaria Massa3, Carlo Bergamini4, Alessandro Trentini4, Giovanni De Rosa5, Lorenzo Daniele5, Fabiola Ciccosanti6, Carlo Cervellati7, Francesco Leone8, Massimo Aglietta3,9. 1. Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy. giuliana.cavalloni@ircc.it. 2. Cancer Genomics Lab, Fondazione Edo ed Elvo Tempia, Biella, Italy. 3. Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy. 4. Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy. 5. Pathology Unit, AO Ordine Mauriziano, Torino, Italy. 6. Department of Epidemiology, Preclinical Research, and Advanced Diagnostics, National Institute for Infectious Diseases, IRCCS 'Lazzaro Spallanzani', Rome, Italy. 7. Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara, Italy. 8. Department of Oncology, ASL BI, Ospedale degli Infermi di Biella, Ponderano, BI, Italy. 9. Department of Oncology, University of Turin, Torino, Italy.
Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line. METHODS: Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues. RESULTS: We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed. CONCLUSIONS: This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.
BACKGROUND:Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line. METHODS: Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues. RESULTS: We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed. CONCLUSIONS: This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.
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