Abstract
Simple SummaryTackling and curing cancer is still one of the most important challenges of biomedical research. Lung cancer is among the most diverse and lethal types, therefore identifying alterations in proteins participating in events leading to this disease is crucial. By analyzing and comparing the tissue proteomics profile of small cell lung cancer, as well as non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) subtypes, following on-surface tryptic digestion, we aimed to identify the key dysregulated pathways. Proteins altered between cancerous and respective adjacent normal tissue were determined to reveal common and lung cancer type-specific changes. These proteins can contribute to a more precise classification of lung cancer and, following validation, can further improve the currently available diagnostic panels.Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis. Principal component analysis clearly distinguished cancerous and cancer adjacent normal samples, while the four lung cancer types investigated had distinct molecular profiles and gene set enrichment analysis revealed specific dysregulated biological processes as well. Furthermore, proteins with altered expression unique to a specific lung cancer type were identified and could be the targets of future studies.
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