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Open Access 01-12-2021 | Cholangiocarcinoma | Research

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

Authors: Giuliana Cavalloni, Caterina Peraldo-Neia, Annamaria Massa, Carlo Bergamini, Alessandro Trentini, Giovanni De Rosa, Lorenzo Daniele, Fabiola Ciccosanti, Carlo Cervellati, Francesco Leone, Massimo Aglietta

Published in: BMC Cancer | Issue 1/2021

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.

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Title: Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients
Authors: Giuliana Cavalloni
Caterina Peraldo-Neia
Annamaria Massa
Carlo Bergamini
Alessandro Trentini
Giovanni De Rosa
Lorenzo Daniele
Fabiola Ciccosanti
Carlo Cervellati
Francesco Leone
Massimo Aglietta
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Cholangiocarcinoma
Cholangiocarcinoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08576-z

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