title: Differentially expressed and activated proteins associated with non small cell lung cancer tissues.
abstract: BACKGROUND
  Lung cancer is a leading cause of mortality. The most common cancer subtype, non small cell lung cancer (NSCLC), accounts for 85-90% all cases and is mainly caused by environmental and genetic factors. Mechanisms involved in lung carcinogenesis include deregulation of several kinases and molecular pathways affecting cell proliferation, apoptosis and differentiation. Despite advances in lung cancer detection, diagnosis and staging, survival rate still remains poor and novel biomarkers for both diagnosis and therapy need to be identified. In the present study, we have explored the potential of novel specific biomarkers in the diagnosis of NSCLC, and the over-expression/activation of several kinases involved in disease development and progression.
  
  
  METHODS
  Lung tumor tissue specimens and adjacent cancer-free tissues from 8 NSCLC patients undergoing surgery were collected. The differential activation status of ERK1/2, AKT and IKBα/NF-κβ was analyzed. Subsequently, protein expression profile of NSCLC vs normal surrounding tissue was compared by a proteomic approach using LC-MS MS. Subsequently, MS/MS outputs were analyzed by the Protein Discoverer platform for label-free quantitation analysis. Finally, results were confirmed by western blotting analysis.
  
  
  RESULTS
  This study confirms the involvement of ERK1/2, AKT, IKBα and NF-κβ proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Furthermore, we found significant differential expression of 20 proteins (Rsc ≥ 1.50 or ≤ -1.50) of which 7 are under-expressed and 13 over-expressed in NSCLC lung tissues. Finally, we validated, by western blotting, the two most under-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms.
  
  
  CONCLUSIONS
  Our data further support the possibility of developing both diagnostic tests and innovative targeted therapy in NSCLC. In addition to selective inhibitors of ERK1/2, AKT, IKBα and NF-κβ, as therapeutic options, our data, for the first time, indicates carbonic anhydrase I and II as attractive targets for development of diagnostic tools enabling selection of patients for a more specific therapy in NSCLC.
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Nigro
authors.affiliation: IRCCS SDN, Via E. Gianturco 113, 80142, Naples, Italy.|Present address: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Imperlini
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.|Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini 5, 80131, Naples, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Scudiero
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Monaco
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Polito
authors.affiliation: Dipartimento di Scienze Cardio-Toraciche e Respiratorie, Seconda Università degli Studi di Napoli, Via L. Bianchi, 80131, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mazzarella
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.|Dipartimento di Scienze Motorie e del Benessere, Università di Napoli Parthenope, Via Amm. F. Acton 38, 80133, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Orrù
authors.affiliation: Cattedra di Malattie dell'Apparato Respiratorio, Dipartimento di Medicina e Scienze per la Salute "V Tiberio", Università del Molise, Via De Sanctis, 86100, Campobasso, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.affiliation: CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy. aurora.daniele@unina2.it.|Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università degli Studi di Napoli, Via G. Vivaldi 42, 81100, Caserta, Italy. aurora.daniele@unina2.it.
authors.forename: A
authors.initials: A
authors.lastname: Daniele
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D009363:Neoplasm Proteins