IADR Abstract Archives

Characterization and validation of immunomic biomarkers in HNSCC

Tumor antigens are proteins selectively expressed by tumor cells and recognized by the host immune system. The humoral response to these antigens is of value in cancer detection and treatment selection. Objective: To detect the humoral response in serum from patients with head and neck squamous cell carcinoma (HNSCC). Methods: Phage libraries displaying cancer antigens were biopanned with sera from 30 HNSCC patients or 30 non-cancer patients. After biopanning, 1152 clones were randomly selected for construction of an immunomic array. These arrays were used to screen 48 HNSCC and 34 control serum samples. Results: The top 96 clones selected by regularized logistic regression, yielded the best performance based on their specificity and sensitivity as measured by the ROC curve. The specificity was 70.6% (95% confidence interval, 52.5-84.9), while sensitivity was 81.3% (95% CI, 67.4-91.0). The 96 clones were sequenced to identify the proteins. Of the 96 clones, 6 were in-frame, 6 were identified by the 5' or 3' sequences and 18 were out of frame. The remaining clones were unidentified proteins. Twenty-one clones were further validated by the Luminex 200 system. The optimal cross-validated ROC curve showed an AUC of 0.715. This indicated the strong predictive potential of this signature. One of these proteins, RPL23, was selected for expression and validation studies. Expression was investigated by qPCR and immunblot analysis of HNSCC cell lines. Relative to normal keratinocytes, RPL23 mRNA is upregulated in ten HNSCC cell lines tested. For functional studies, RPL23 expression in 3 HNSCC cell lines that strongly express the protein was downregulated by siRNA. Knockdown of RPL23 inhibited proliferation and invasion. Overexpression of RPL23 had the reverse effect on proliferation. Conclusions: Thus, RPL23 promotes the tumorigenic phenotype in HNSCC cells. (This work was supported by NIDCR DE017977, DE019513, NCI SPORE grant P50 CA97248, MICHR CTSA UL1RR024986).
IADR/AADR/CADR General Session
2011 IADR/AADR/CADR General Session (San Diego, California)
San Diego, California
2011
73
Oral Medicine & Pathology
  • Liu, Min  ( University of Michigan, Ann Arbor, MI, USA )
  • D'silva, Nisha  ( University of Michigan, Ann Arbor, MI, USA )
  • Wang, Xiaojuw  ( University of Michigan, Ann Arbor, MI, USA )
  • Russo, Nickole  ( University of Michigan, Ann Arbor, MI, USA )
  • Banerjee, Rajat  ( University of Michigan, Ann Arbor, MI, USA )
  • Goto, Mitsuo  ( University of Michigan, Ann Arbor, MI, USA )
  • Tsodikov, Alexander  ( University of Michigan, Ann Arbor, MI, USA )
  • Duffy, Sonia  ( University of Michigan, Ann Arbor, MI, USA )
  • Wolf, Greg  ( University of Michigan, Ann Arbor, MI, USA )
  • Chinnaiyan, Arul  ( University of Michigan, Ann Arbor, MI, USA )
    • Oral Session
    Oral Carcinogenesis
    03/16/2011