A ProteomicsDriven Assay Denes Specic Plasma Protein Signatures in Different Stages of Ménière 0 s Disease G. Chiarella, 1 M. Di Domenico, 2,3 ** C. Petrolo, 1 M. Saccomanno, 4 R. Rothenberger, 3 A. Giordano, 3 F. Costanzo, 4 E. Cassandro, 5 and G. Cuda 4 * 1 Audiology and Phoniatrics Unit, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy 2 Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Naples, Italy 3 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania 4 Department of Experimental and Clinical Medicine, Laboratory of Proteomics and Mass Spectrometry, Magna Graecia University of Catanzaro, Catanzaro, Italy 5 Department of Medicine, University of Salerno, Salerno, Italy ABSTRACT Ménière 0 s disease (MD) is a common disorder of the inner ear whose hallmarks are vertigo, tinnitus, aural fullness, and progressive hearing loss. The degree of severity of the disease is quite heterogeneous, and so is its pathogenesis. A multifactorial inheritance of intrinsic and extrinsic factors has been described, but there is not a common agreement on the molecular basis of MD. In a recent article, we have demonstrated that patients suffering from MD share a common plasma proteomic signature, characterized by the presence of several upand downregulated proteins. In this study, we have further extended our analysis and show that the differential expression of plasma proteins can identify specic subsets of MDaffected individuals, depending on their stage. Our ndings conrm our plasma proteomicsdriven approach as a powerful tool for early diagnosis of MD and uncover a potentially starring role for some proteins in the development and fate of this frustrating disease, whose pathogenesis still remains unclear. J. Cell. Biochem. 115: 10971100, 2014. ß 2013 Wiley Periodicals, Inc. KEY WORDS: MÉNIÈRE 0 s DISEASE; PROTEOMICS; TWODIMENSIONAL GEL ELECTROPHORESIS; MASS SPECTROMETRY; HUMANS, BIOMARKERS DISCOVERY F irst described in Ménière [1861] MD is clinically characterized by episodic vertigo, uctuating hearing loss, aural fullness and tinnitus. MD is disabling, signicantly affecting quality of life, and often fallouts in clinical depression. The epidemiology of the disorder is still not clearly dened. Prevalence rates of MD have varied widely, ranging from 3.5 per 100,000 to 513 per 100,000 [Alexander and Harris, 2010], with more recent data accounting for 190 per 100,000 [Harris and Alexander, 2010]. Such a broad range is likely due to methodological differences, changes over time in diagnostic criteria, difculty in differential diagnosis from related conditions. MD is more likely to occur in women and the prevalence increases with aging [Alexander and Harris, 2010]. Despite many years of research, the exact causes, pathophysiology and treatments of MD still remain elusive. Histologically, postmortem examination reveals endolymphatic hydrops [Hallpike and Cairns, 1938; Yamakawa, 1938]. The American Academy of OtolaryngologyHead and Neck Surgery (AAOHNS) Hearing and Equilibrium Subcommittee has published guidelines for the classication and reporting of MD. These guidelines, which specify character, frequency, and duration of vertigo attacks necessary to achieve a diagnosis of MD, have been Abbreviation: MD, Ménière disease. The authors declare that they have no conict of interest. * Correspondence to: Giovanni Cuda, Department of Experimental and Clinical Medicine, Laboratory of Proteomics and Mass Spectrometry, Magna Graecia University of Catanzaro, Campus Universitario S. Venuta, Germaneto, Catanzaro 88100, Italy. Email: cuda@unicz.it ** Correspondence to: Marina Di Domenico, Department of Biochemistry, Biophysics, and General Pathology, Second University of Naples, Naples, Italy. Email: marina.didomenico@unina2.it Manuscript Received: 20 November 2013; Manuscript Accepted: 10 December 2013 Accepted manuscript online in Wiley Online Library (wileyonlinelibrary.com): 19 December 2013 DOI 10.1002/jcb.24747 ß 2013 Wiley Periodicals, Inc. 1097 Journal of Cellular Biochemistry ARTICLE Journal of Cellular Biochemistry 115:1097–1100 (2014)