Beta-defensin index: A functional biomarker for oral cancer detection
Santosh K. Ghosh, Yuncheng Man, Arwa Fraiwan, Christopher Waters, C. G. McKenzie, Cheng Lu, David Pfau, Hameem I. Kawsar, Natarajan Bhaskaran, Pushpa Pandiyan, Ge Jin, Farren Briggs, Chad C. Zender, Rod Rezaee, Fotinos Panagakos, Jason E. Thuener, Jay Wasman, Alice L. Tang, Hiba Qari, Trisha M. Wise‐Draper, Thomas S. McCormick, Anant Madabhushi, Umut A. Gürkan, Aaron Weinberg
Abstract
There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.