title: Quantitative proteomic analysis of oral brush biopsies identifies secretory leukocyte protease inhibitor as a promising, mechanism-based oral cancer biomarker.
abstract: A decrease in the almost fifty percent mortality rate from oral cancer is needed urgently. Improvements in early diagnosis and more effective preventive treatments could affect such a decrease. Towards this end, we undertook for the first time an in-depth mass spectrometry-based quantitative shotgun proteomics study of non-invasively collected oral brush biopsies. Proteins isolated from brush biopsies from healthy normal tissue, oral premalignant lesion tissue (OPMLs), oral squamous cell carcinoma (OSCC) and matched control tissue were compared. In replicated proteomic datasets, the secretory leukocyte protease inhibitor (SLPI) protein stood out based on its decrease in abundance in both OPML and OSCC lesion tissues compared to healthy normal tissue. Western blotting in additional brushed biopsy samples confirmed a trend of gradual decreasing SLPI abundance between healthy normal and OPML tissue, with a larger decrease in OSCC lesion tissue. A similar SLPI decrease was observed in-vitro comparing model OPML and OSCC cell lines. In addition, exfoliated oral cells in patients' whole saliva showed a loss of SLPI correlated with oral cancer progression. These results, combined with proteomics data indicating a decrease in SLPI in matched healthy control tissue from OSCC patients compared to tissue from healthy normal tissue, suggested a systemic decrease of SLPI in oral cells correlated with oral cancer development. Finally, in-vitro experiments showed that treatment with SLPI significantly decreased NF-kB activity in an OPML cell line. The findings indicate anti-inflammatory activity in OPML, supporting a mechanistic role of SLPI in OSCC progression and suggesting its potential for preventative treatment of at-risk oral lesions. Collectively, our results show for the first time the potential for SLPI as a mechanism-based, non-invasive biomarker of oral cancer progression with potential in preventive treatment.
authors.affiliation: Department of General Dentistry, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Oral Medicine, Diagnosis and Radiology, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Rhodus
authors.affiliation: Department of Otolaryngology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
authors.affiliation: Department of Otolaryngology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Beverly R K
authors.initials: BR
authors.lastname: Wuertz
authors.affiliation: Department of Oral Medicine, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Dentistry, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Griffin
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D017930:Genes, Reporter; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism*; D040901:Proteomics; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D053481:Secretory Leukocyte Peptidase Inhibitor
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