2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma
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Giada Poli1,*, Elisabetta Ceni2,*, Roberta Armignacco1, Tonino Ercolino3, Letizia Canu1, Gianna Baroni4, Gabriella Nesi4, Andrea Galli2, Massimo Mannelli1,5 and Michaela Luconi1,5
1 Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
2 Gastroenterology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
3 Endocrinology Unit, Careggi Hospital, Azienda Ospedaliera Universitaria Careggi, Florence, Italy
4 Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
5 Istituto Toscano Tumori, Florence, Italy
* These authors contributed equally to this work
Michaela Luconi, email:
Massimo Mannelli, email:
Keywords: proteomics, cancer metabolism, biomarkers
Received: December 02, 2014 Accepted: January 02, 2015 Published: January 21, 2015
Adrenocortical carcinoma (ACC) is a rare aggressive tumor with poor prognosis when metastatic at diagnosis. The tumor biology is still mostly unclear, justifying the limited specificity and efficacy of the anti-cancer drugs currently available. This study reports the first proteomic analysis of ACC by using two-dimensional-differential-in-gel-electrophoresis (2D-DIGE) to evaluate a differential protein expression profile between adrenocortical carcinoma and normal adrenal. Mass spectrometry, associated with 2D-DIGE analysis of carcinomas and normal adrenals, identified 22 proteins in 27 differentially expressed 2D spots, mostly overexpressed in ACC. Gene ontology analysis revealed that most of the proteins concurs towards a metabolic shift, called the Warburg effect, in adrenocortical cancer. The differential expression was validated by Western blot for Aldehyde-dehydrogenase-6-A1,Transferrin, Fascin-1,Lamin A/C,Adenylate-cyclase-associated-protein-1 and Ferredoxin-reductase. Moreover, immunohistochemistry performed on paraffin-embedded ACC and normal adrenal specimens confirmed marked positive staining for all 6 proteins diffusely expressed by neoplastic cells, compared with normal adrenal cortex.
In conclusion, our preliminary findings reveal a different proteomic profile in adrenocortical carcinoma compared with normal adrenal cortex characterized by overexpression of mainly metabolic enzymes, thus suggesting the Warburg effect also occurs in ACC. These proteins may represent promising novel ACC biomarkers and potential therapeutic targets if validated in larger cohorts of patients.
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