Glycoproteomics Analysis of Triple Wild-Type Lung Adenocarcinoma Tissue Samples

Lung cancer has both high incidence and mortality, making it the leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease, with several histological subtypes and genetic alterations that influence prognosis and available treatment options. Here, we focus on the triple wild-type (TWT) subtype of lung adenocarcinoma (LUAD) that lacks the three most common actionable genetic alterations, subsequently making targeted therapies inaccessible. In this study, our aim was the mass spectrometry-based proteomic and N-glycoproteomic characterization of tumor and adjacent normal lung tissue regions from individuals (n = 12) with TWT LUAD. We found several proteins previously identified as potential prognostic or diagnostic biomarkers in LUAD and described dysregulated biological processes, giving an overview of the general differences between healthy and tumor tissue. Also, we highlight specific signatures detected using N-glycoproteomics and discuss their potential and importance based on data from databases and literature. To the best of our knowledge, this is the first N-glycoproteomics-focused study on TWT LUAD, and it could provide a valuable resource for further studies into this less well characterized subtype of lung cancer. For instance, we report altered N-glycosylation for several glycoproteins implicated in LUAD and other cancers that could have functional importance connected to the disease.