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A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature

Oncogene volume 32, pages 5026–5037 (2013)Cite this article

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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.

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Acknowledgements

The authors would like to thank Kenneth Rieger for his artistic assistance with illustrations. This work was supported by NIDCR DE017977, DE019513, MICHR CTSA UL1RR024986, Research Development award from NCI SPORE grant P50 CA97248 (NJD). This research was made possible, in part, by the use of the Cancer Center Flow Cytometry Core which was supported (in part) by the National Institutes of Health through the University of Michigan’s Cancer Center Support Grant (5 P30 CA46592).

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Authors and Affiliations

  1. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA

    N Russo, M Liu, R Banerjee, M Goto, C Scanlon, T Metwally, R C Inglehart, E Van Tubergen & N J D’Silva

  2. Department of Pathology, University of Michigan, Ann Arbor, MI, USA

    X Wang, A M Chinnaiyan & N J D’Silva

  3. Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA

    X Wang, A M Chinnaiyan & N J D’Silva

  4. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA

    A Tsodikov

  5. Medical School, School of Nursing, University of Michigan, Ann Arbor, MI, USA

    S Duffy

  6. Department of Otolaryngology, University of Michigan, Ann Arbor, MI, USA

    C Bradford, T Carey & G Wolf

  7. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    A M Chinnaiyan

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  1. N Russo
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Correspondence to N J D’Silva.

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Competing interests

Dr Chinnaiyan is a co-founder of Compendia Biosciences, which supports the Oncomine database used in this study. Compendia Biosciences is a wholly owned subsidiary of Life Technologies, in which Dr Chinnaiyan serves on the Medical Advisory Board. Life Technologies and/or Compendia Biosciences did not play a role in the design and conduct of this study, in the collection, analysis or interpretation of the data, or in the preparation, review or approval of the article.

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Russo, N., Wang, X., Liu, M. et al. A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature. Oncogene 32, 5026–5037 (2013). https://doi.org/10.1038/onc.2012.532

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