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PLoS One

Title:		Feasibility of integrating canine olfaction with chemical and microbial profiling of urine to detect lethal prostate cancer
Author(s):		Guest C; Harris R; Sfanos KS; Shrestha E; Partin AW; Trock B; Mangold L; Bader R; Kozak A; McLean S; Simons J; Soule H; Johnson T; Lee WY; Gao Q; Aziz S; Stathatou PM; Thaler S; Foster S; Mershin A;
Address:		"Medical Detection Dogs, Milton Keynes, United Kingdom. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Cambridge Polymer Group, Cambridge, Massachusetts, United States of America. Prostate Cancer Foundation, Santa Monica, California, United States of America. Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, Texas, United States of America. The Center for Bits and Atoms, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America. Imagination Engines, St. Charles, Missouri, United States of America. Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America"
Journal Title:		PLoS One
Year:		2021
Volume:		20210217
Issue:		2
Page Number:		e0245530 -
DOI:		10.1371/journal.pone.0245530
ISSN/ISBN:		1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:		"Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs' diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples"
Keywords:		"Animals Biomarkers, Tumor/*urine Dogs Feasibility Studies Male Pilot Projects Prostatic Neoplasms/*diagnosis *Smell Urinary Tract/*microbiology Volatile Organic Compounds/*urine;"
Notes:		"MedlineGuest, Claire Harris, Rob Sfanos, Karen S Shrestha, Eva Partin, Alan W Trock, Bruce Mangold, Leslie Bader, Rebecca Kozak, Adam Mclean, Scott Simons, Jonathan Soule, Howard Johnson, Thomas Lee, Wen-Yee Gao, Qin Aziz, Sophie Stathatou, Patritsia Maria Thaler, Stephen Foster, Simmie Mershin, Andreas eng SC1 CA245675/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2021/02/18 PLoS One. 2021 Feb 17; 16(2):e0245530. doi: 10.1371/journal.pone.0245530. eCollection 2021"