Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients

BMC Cancer

Caterina Peraldo-Neia¹  Carlo Bergamini²  Alessandro Trentini²  Fabiola Ciccosanti³  Carlo Cervellati⁴  Francesco Leone⁵  Massimo Aglietta⁶  Annamaria Massa⁶  Giuliana Cavalloni⁶  Lorenzo Daniele⁷  Giovanni De Rosa⁷ 

[1] Cancer Genomics Lab, Fondazione Edo ed Elvo Tempia;Department of Chemistry and Pharmaceutical Sciences, University of Ferrara;Department of Epidemiology, Preclinical Research, and Advanced Diagnostics, National Institute for Infectious Diseases, IRCCS ‘Lazzaro Spallanzani’;Department of Morphology, Surgery & Experimental Medicine, University of Ferrara;Department of Oncology, ASL BI, Ospedale degli Infermi di Biella;Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS;Pathology Unit, AO Ordine Mauriziano;

关键词: Intrahepatic cholangiocarcinoma;    Proteomics;    Mass spectrometry;    Metabolism;    ROS;   

DOI  :  10.1186/s12885-021-08576-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown