Lung cancer is an increasing widespread leading cause of death. The most common cancer subtype, the non small cell lung cancer (NSCLC), accounts for 85%-90% of all cases. NSCLC is mainly due to environmental and genetic factors are. At cellular level, derangement in the regulation of proliferation, apoptosis and differentiation are determinant cellular processes involved in lung carcinogenesis; these processes are distinguished by deregulation of several kinases and molecular pathways. Sticking advances have been performed in lung cancer detection diagnosis and staging but actually novel biomarkers need to be found. In the present study, we investigated the possibility to identify novel specific biomarkers for the diagnosis of NSCLC, and the over-expression of several kinases involved in development and progression of NSCLC. Method We collected tumor lung surgery specimens and their adjacent normal tissues from 8 NSCLC patients. We analyzed and compared activation status of ERK1/2, AKT and IKB/NF-. Successively, we compared protein expression profile of NSCLC tissues vs relative control lung tissues by a proteomic approach using LC-MS MS. Successively, we analyzed MS/MS outputs by the Protein Discoverer platform and submitted them to label-free quantitation analysis. Finally, we confirmed our results by western blotting analysis. Results This study confirms the involvement of ERK1/2, AKT, IKB and NF- proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Moreover, 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 over-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms. Conclusion Our data encourage the possibility to find reliable tools for the development of novel drugs for lung cancer treatment such as selective inhibitors of ERK1/2, AKT, IKB and NF-to further perzonalize therapy in NCLC. Moreover, carbonic anhydrase I and II, the two most over-expressed proteins between NSCLC and relative control lung tissues, seem to be very interesting opportunities for the development of potential novel diagnostic biomarkers and/or to select patients for NSCLC therapy.

Differentially expressed and activated proteins associated with non small cell lung cancer tissues

IMPERLINI, Esther;ORRU', STEFANIA;
2015

Abstract

Lung cancer is an increasing widespread leading cause of death. The most common cancer subtype, the non small cell lung cancer (NSCLC), accounts for 85%-90% of all cases. NSCLC is mainly due to environmental and genetic factors are. At cellular level, derangement in the regulation of proliferation, apoptosis and differentiation are determinant cellular processes involved in lung carcinogenesis; these processes are distinguished by deregulation of several kinases and molecular pathways. Sticking advances have been performed in lung cancer detection diagnosis and staging but actually novel biomarkers need to be found. In the present study, we investigated the possibility to identify novel specific biomarkers for the diagnosis of NSCLC, and the over-expression of several kinases involved in development and progression of NSCLC. Method We collected tumor lung surgery specimens and their adjacent normal tissues from 8 NSCLC patients. We analyzed and compared activation status of ERK1/2, AKT and IKB/NF-. Successively, we compared protein expression profile of NSCLC tissues vs relative control lung tissues by a proteomic approach using LC-MS MS. Successively, we analyzed MS/MS outputs by the Protein Discoverer platform and submitted them to label-free quantitation analysis. Finally, we confirmed our results by western blotting analysis. Results This study confirms the involvement of ERK1/2, AKT, IKB and NF- proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Moreover, 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 over-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms. Conclusion Our data encourage the possibility to find reliable tools for the development of novel drugs for lung cancer treatment such as selective inhibitors of ERK1/2, AKT, IKB and NF-to further perzonalize therapy in NCLC. Moreover, carbonic anhydrase I and II, the two most over-expressed proteins between NSCLC and relative control lung tissues, seem to be very interesting opportunities for the development of potential novel diagnostic biomarkers and/or to select patients for NSCLC therapy.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11367/38318
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