Author: Shen Hu, Lifeng Zhang, Jiang Jiang, Martha Arellano-Garcia, and David Wong

Abstract: The stagnant survival rates over the past few decades for patients with oral/head and neck squamous cell carcinoma (OSCC/HNSCC) emphasize the need for identifying novel diagnostic and therapeutic targets based on molecular profiling of the tumor. In this study, we have conducted patient-based proteomic analysis towards the discovery of potential serum and tissue protein targets associated with OSCC/HNSCC. First, we have utilized quantitative proteomics based on gel electrophoresis and stable isotope labeling/tandem mass spectrometry (MS/MS) to identify differentially expressed serum proteins between lymph-node metastatic and non-metastatic OSCCs. Proteins in PAGE gel bands were digested and the resulting peptides were labeled with iTRAQ reagents and subsequently quantified with liquid chromatography (LC) with quadrupole time-of-flight MS or linear ion trap MS (LTQ). The differentially expressed proteins included transthyretin, alpha-fibrinogen, tetranectin, hemopexin, ficolin, HGF activator, plasminogen, clusterin, etc. Second, we have performed comparative proteomic analysis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs because HPV has been recognized as an important risk factor for a subset of OSCC/HNSCC. Differentially expressed proteins were revealed by 2-D gel electrophoresis and then identified using in-gel tryptic digestion followed by LC-MS/MS (linear ion trap). Interesting targets associated with HPV-positive HNSCC included NHEJ1, PARK7 (oncogene DJ-1), superoxide dismutase, heat shock protein beta-1, fatty acid-binding protein, etc. NHEJ1 is a DNA repair protein involved in DNA nonhomologous end joining whereas PARK7 acts as a positive regulator of androgen receptor-dependent transcription and has cell-growth promoting and transforming activities. In addition, we have profiled the E6- and E7-binding proteins within HPV-positive and HPV-negative HNSCC tissues using immunoprecipitation and LC-MS/MS. Apart from helping us to understand the molecular mechanism of the cancer diseases, these protein targets may also have potential clinical applications such as biomarkers if further validated.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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