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Differentially expressed and activated proteins associated with non small cell lung cancer tissues
E Nigro1, E Imperlini2,3, O Scudiero1,4
1CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
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.
Method:
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.
Conclusion:
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.
Insights
This study identifies novel biomarkers for non-small cell lung cancer (NSCLC) diagnosis and therapy. Carbonic anhydrase I and II are highlighted as promising targets for NSCLC patient selection and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality, driven by genetic and environmental factors.
- Dysregulated kinase pathways are implicated in lung carcinogenesis, yet effective diagnostic and therapeutic biomarkers remain elusive.
- Identifying novel biomarkers is crucial for improving NSCLC patient outcomes.
Purpose of the Study:
- To explore novel biomarkers for NSCLC diagnosis.
- To investigate the role of specific kinases (ERK1/2, AKT, IKBα/NF-κB) in NSCLC development and progression.
- To compare protein expression profiles in NSCLC versus normal lung tissue.
Main Methods:
- Analysis of kinase activation (ERK1/2, AKT, IKBα/NF-κB) in NSCLC tissues.
- Proteomic analysis using Liquid Chromatography-Mass Spectrometry (LC-MS/MS) for differential protein expression.
- Validation of key protein findings using Western blotting.
Main Results:
- Significant over-activation of ERK1/2, AKT, IKBα, and NF-κB proteins in NSCLC confirmed.
- Differential expression of 20 proteins identified, with 7 under-expressed and 13 over-expressed in NSCLC.
- Carbonic anhydrase I and II isoforms validated as significantly under-expressed in NSCLC tissues.
Conclusions:
- Findings support the development of diagnostic tests and targeted therapies for NSCLC.
- Carbonic anhydrase I and II represent novel therapeutic targets for NSCLC patient stratification.
- Targeted inhibitors of ERK1/2, AKT, IKBα, and NF-κB offer potential therapeutic strategies.
