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Diagnostic Technologies and Molecular and Cellular Profiling: Biomarkers in Early Detection and Diagnosis

Psoriasin (S100A7) identified as a biomarker in oral squamous cell carcinoma using a proteomic approach

University of California, San Francisco, CA

Abstract

A16

Introduction: Epithelial dysplasia is the primary risk factor for oral cancer; however, most dysplastic lesions never progress to cancer. For patients with dysplasia, there are no predictive markers of progression. The goal of this preliminary study is to use proteomics to discover biomarkers for dysplasia progression.Methods: We utilized frozen tissue samples of site matched temporally distinct normal epithelium and squamous cell carcinoma (SCC) from 1 patient and site matched temporally distinct low grade dysplasia (LGD) and carcinoma in situ (CIS) from another patient. All cases occurred on the tongue. Lesional tissue was microdissected, proteins extracted and separated by two-dimensional gel electrophoresis. The gels were stained with Colloidal Coomassie and imaged using ImageMaster 2D Platinum software. Comparing gels from LGD and CIS samples, we detected 306 and 360 protein spots respectively. Among them, 196 common spots were matched by location on the gel. For comparison between normal tissue and SCC, 303 and 244 spots were detected respectively where 224 spots were present in both. Using the spot volume as a parameter in ImageMaster 2D Platinum software and limiting the analysis to less than 35 kDa proteins, we identified spots with different protein levels. We performed in-gel trypsin digestion to those protein spots, provisionally identified them by peptide mass fingerprinting (MALDI TOF MS) and confirmed their identification using LC MS/MS.Results: Comparing LGD to CIS: fatty acid binding protein 5 (FABP-5), calgranulin B (S100 A9), psoriasin, annexin A2 and galectin-7 were identified to have higher levels of protein in CIS than in LGD. Comparing normal to SCC: superoxide dismutase, alpha-cyrstallin B, creatine kinase, troponins, annexin, calgranulin A (S100 A8), psoriasin and galectin-7 were identified having higher protein levels in SCC than in normal. To confirm and localize differentially regulated proteins, we stained by immunohistochemistry 10 cases of hyperkeratosis, dysplasia, CIS, and SCC for fatty acid binding protein 5 and psoriasin. We found FABP-5 to be highly expressed but without specificity to the different tissue layers. By contrast, psoriasin protein was weakly and focally expressed in normal epithelium but strongly and diffusely expressed in high grade dysplasias and SCC.Discussion: We have used proteomics to identify candidate protein biomarkers involved in progression of dysplasia to SCC. Psoriasin, reported recently to be regulated at transcriptional level in oral SCC cell lines, was identified at high levels in high grade dysplasia and SCC and may be a biomarker of dysplasia progression.