Details

Autor(en) / Beteiligte

• Ghosh, Santosh K.
• Man, Yuncheng
• Fraiwan, Arwa
• Waters, Christopher
• McKenzie, Crist
• Lu, Cheng
• Pfau, David
• Kawsar, Hameem
• Bhaskaran, Natarajan
• Pandiyan, Pushpa
• Jin, Ge
• Briggs, Farren
• Zender, Chad C.
• Rezaee, Rod
• Panagakos, Fotinos
• Thuener, Jason E.
• Wasman, Jay
• Tang, Alice
• Qari, Hiba
• Wise-Draper, Trisha
• McCormick, Thomas S.
• Madabhushi, Anant
• Gurkan, Umut A.
• Weinberg, Aaron

Titel

Beta-defensin index: A functional biomarker for oral cancer detection

Ist Teil von

• Cell reports. Medicine, 2024-03, Vol.5 (3), p.101447-101447, Article 101447

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •The beta-defensin index (BDI) non-invasively distinguishes OSCC from benign lesions•BDI calculates hBD3 (over)expression/hBD2 (under)expression to detect CIS and OSCC•A multi-center validation study yields sensitivity and specificity of 98% and 83%•The BDI may be adapted to a point-of-care assay using intact cell microfluidics Ghosh et al. present a non-invasive ELISA-based beta-defensin index (BDI) detection platform for oral squamous cell carcinoma (OSCC). Blinded discovery and validation studies demonstrate that BDI can discriminate OSCC from benign lesions. A proof-of-principle study shows promise in transforming BDI into a microfluidic intact cell assay for future point-of-care application.