title: 2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma.
abstract: 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.
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Poli
authors.affiliation: Gastroenterology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ceni
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Armignacco
authors.affiliation: Endocrinology Unit, Careggi Hospital, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Canu
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.affiliation: Gastroenterology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.|Istituto Toscano Tumori, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.|Istituto Toscano Tumori, Florence, Italy.
authors.forename: Michaela
authors.initials: M
authors.lastname: Luconi
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy; D018268:Adrenocortical Carcinoma / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; cancer metabolism; proteomics