The investigation of post-translational modifications for the discovery of candidate biomarkers in NON-small cell lung cancer

Nowadays, mass spectrometer-based proteomic approaches have become powerful tools for detecting differences in the physiological and pathological processes of the cell and for clarifying the molecular development and course of disease. In this respect, MS-based phosphoproteomics plays an important role in the elucidation of irregular pathways and functional proteins in cancer development in more detail. In this study, we aimed to determine phosphoproteomic profiles in control and tumor tissues of patients with large cell carcinoma (LCC), a rare subtype of non-small cell lung carcinomas (NSCLC). The patient tissues of this subtype, where there are very few studies in the literature, were first prepared in accordance with the label-free relative quantification, and then mass spectrometry analyzes were performed in discovery mode. The obtained phosphoproteomic profiles were examined with the help of powerful informatics programs and significant expression differences were revealed. Thus, a total of 2314 phosphoproteins have been identified and 2194 of them have been quantified with high confidence. Of the 324 phosphoproteins with at least two-fold changes in expression, 156 were significantly up-regulated and 168 were down-regulated. A number of these phosphoproteins were selected for validation and re-analyzed by targeted proteomic approach. In this way, unlike traditional methods, over 70 proteins were examined more precisely in a very short time and at a much less cost and the expression differences between the groups were verified. In this study, for the first time in our country, detailed phosphoproteomic data about the LCC (and NSCLC) was obtained. To our knowledge, this is the first large-scale phosphoproteomic study, in which LCC tumor tissues were examined against their own healthy tissues, significant differences were revealed related to the disease and expression differences were verified with a MS-based method again.