Enhanced Interferon Signaling Pathway in Oral Cancer Revealed by Quantitative Proteome Analysis of Microdissected Specimens Using 16O/18O Labeling and Integrated Two-dimensional LC-ESI-MALDI Tandem MS

摘要: Oral squamous cell carcinoma (OSCC) remains one of the most common cancers worldwide, and mortality rate this disease has increased in recent years. No molecular markers are available to assist with early detection therapeutic evaluation OSCC; thus, identification differentially expressed proteins may potential shed light on mechanisms OSCC pathogenesis. We performed a multidimensional 16O/18O proteomics analysis using an integrated ESI-ion trap MALDI-TOF/TOF MS system computational data pipeline identify that microdissected tumor cells relative adjacent non-tumor epithelia. identified 1233 unique oral epithelia obtained from three pairs specimens false discovery <3%. Among these, 977 were quantified between cells. Our revealed 80 dysregulated (53 up-regulated 27 down-regulated) when 2.5-fold change was used as threshold. Immunohistochemical staining Western blot analyses confirm overexpression 12 tissues. When biological roles assessed via MetaCore™ analysis, interferon (IFN) signaling pathway emerged significantly altered pathways OSCC. As many 20% (10 53) belonged IFN-stimulated gene (ISG) family, including ubiquitin cross-reactive protein (UCRP)/ISG15. Using head-and-neck cancer tissue microarrays, we determined UCRP is overexpressed majority cheek tongue several cases larynx cancer. In addition, found IFN-β stimulates expression enhances their motility vitro. findings new pathogenesis provide basis for future development novel biomarkers.