title: A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature.
abstract: Despite the dismal prognosis for patients with squamous cell carcinoma of the head and neck (SCCHN), there have been no novel treatments in over 40 years. Identification of novel tumor antigens in SCCHN will facilitate the identification of potential novel treatment targets. Tumor antigens are proteins selectively expressed by tumor cells and recognized by the host immune system. Phage-displayed tumor antigens were enriched by biopanning with normal and then SCCHN-specific serum. Ninety-six phage clones were sequenced for identification, and 21 clones were validated using Luminex. One of these proteins, L23, a novel tumor antigen in SCCHN, was validated as an oncogene. L23 is upregulated in SCCHN compared with normal keratinocytes. Knockdown of L23 inhibited proliferation, invasion and cell survival. Overexpression of L23 had the reverse effect. Overexpression of L23 in non malignant cells led to transformation. Injection of SCCHN cells with knockdown of L23 in mice, induced tumors that were significantly smaller than control tumors. In conclusion, the immunomic screen yielded a panel of antigens specific to SCCHN; one of these proteins, L23, is a novel oncogene in SCCHN.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Russo
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Banerjee
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: C
authors.initials: C
authors.lastname: Scanlon
authors.forename: T
authors.initials: T
authors.lastname: Metwally
authors.forename: R C
authors.initials: RC
authors.lastname: Inglehart
authors.forename: A
authors.initials: A
authors.lastname: Tsodikov
authors.forename: S
authors.initials: S
authors.lastname: Duffy
authors.forename: E
authors.initials: E
authors.lastname: Van Tubergen
authors.forename: C
authors.initials: C
authors.lastname: Bradford
authors.forename: T
authors.initials: T
authors.lastname: Carey
authors.forename: G
authors.initials: G
authors.lastname: Wolf
authors.forename: A M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: N J
authors.initials: NJ
authors.lastname: D'Silva
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D001323:Autoantibodies / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D061505:Cell Surface Display Techniques; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009857:Oncogenes; D012016:Reference Values; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000235:genetics* / Q000276:immunology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D012269:Ribosomal Proteins; C032493:ribosomal protein L17