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

delete2024-03-01
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OA
AI
S
Santosh K. Ghosh
Y
Yuncheng Man
A
Arwa Fraiwan
C
Christopher Waters
C
C. G. McKenzie
C
Cheng Lu
D
David Pfau
H
Hameem I. Kawsar
N
Natarajan Bhaskaran
P
Pushpa Pandiyan
G
Ge Jin
F
Farren Briggs
C
Chad C. Zender
R
Rod Rezaee
F
Fotinos Panagakos
J
Jason E. Thuener
J
Jay Wasman
A
Alice L. Tang
H
Hiba Qari
T
Trisha M. Wise‐Draper
T
Thomas S. McCormick
A
Anant Madabhushi
U
Umut A. Gürkan
A
Aaron Weinberg *
DOI:10.1016/j.xcrm.2024.101447delete
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Abstract

Abstract

En 中文
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.
Keywords:
SQUAMOUS-CELL CARCINOMA
GROWTH-FACTOR RECEPTOR
HUMAN BETA-DEFENSIN-1
POTENTIAL APPLICATIONS
TUMOR-SUPPRESSOR
GENE-EXPRESSION
MESSENGER-RNA
CAVITY CANCER
HEAD
BRUSH
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Cell Reports Medicine cover
Cell Reports Medicine
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10.6
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U
University System of Ohio
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University of Cincinnati
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Case Western Reserve University
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