Takaaki Sato,Mitsuo Nonomura,Kimihiko Yoneda,Sho Mizutani,Yoichi Mizutani,
Prostate Cancer-Induced Changes in Urinary Odors at Biomarker Concentrations  of PPQ with Validation by Sniffer Mouse Behavioural Assays
International Journal of Cancer Science and Therapy
2021

http://dx.doi.org/10.31487/j.IJCST.2021.01.02
https://www.sciencerepository.org/prostate-cancer-induced-changes-in-urinary-odors-at-biomarker-concentrations_IJCST-2021-1-102 
Abstract: Although prostate-specific antigen (PSA) is a significant tumor marker for prostate cancer at present, the 
low specificity (approximately 33%) and so on likely lead to an overdiagnosis and patient suffering from 
highly invasive prostate biopsy. Complementary measures with cancer-characteristic biomarkers could 
improve the specificity and accuracy of diagnosis before the biopsy. Previously, “sniffer mice” were shown 
to be super-sensitive to differences in odors and to discriminate between odors of urine mixtures from 
patients with bladder cancer before and after tumor resection as well as urine odors of mice with or without 
experimental tumors. Here, we showed that the sniffer mice discriminate efficiently urinary odors of patients 
with prostate cancer using an odor plume-guided Y-maze behavioural assay. Through discrimination 
training in forced-odor choice, statistically significant increases in correct odor choice rates showed the 
super-sensitivity of sniffer mice to the olfactory cue of ppq-level urinary biomarkers for prostate cancer in 
106
-fold diluted urine samples, where donor-unique odors were below the threshold. Moreover, we validated 
eight volatile urinary biomarkers nearly at their original relative concentrations as the prostate cancer cue 
even when adding a similar biomarker profile to the post-radical prostatectomy urine samples by the same 
behavioural score of the sniffer mice. These biomarkers and profiles could be useful for non-invasive tests 
for prostate and bladder cancers.Keywords: Cancer biomarker, sniffer mouse, body odor disorder, behaviour assay, odor discrimination, non-invasive test