Potential markers of lymph node metastasis in human oral tongue squamous cell carcinoma identified by quantitative tandem mass spectrometry

Objectives: Worldwide, some oral cancers are amongst the most rapidly increasing cancers due to changes in lifestyle. The aim of this prospective study was to identify proteins associated with advancement of oral tongue squamous cell carcinoma (OTSCC). All specimens were compared to identify up- and down-regulated proteins by quantitative proteomics.
Methods: Tongue biopsies were collected from patients at SKMCH&RC and Services Hospital, Pakistan. For each sample, total proteins were extracted, trypsin digested, iTRAQ labeled, combined and separated using SCX chromatography prior to nHPLC-MALDI-MS. Peptide fragment mass lists were searched using Mascot software (Matrix Science, U.K.) against Swiss-Prot database.
Results: Database searching resulted in the identification of 565 proteins (95% confidence interval threshold, p<0.05, Mascot score ≥ 29) with at least 2 signature peptides. A number of stage-specific up- and down-regulated proteins were identified that have not previously been associated with oral tongue squamous cell carcinoma. Of particular importance were those associated with epigenetic, apoptotic and stromal functions of squamous cells and are currently the subjects of further validation as therapeutic targets and diagnostic markers.
Conclusions: Oral cancer represents a heterogeneous group of diseases emerging with both anatomical and stage-specific differences. Our study represents the first attempt to focus on tongue-specific cancer progression in order to identify unique phenotypic markers and targets.