Prostate Cancer-Induced Changes in Urinary Odors at Biomarker Concentrations of PPQ with Validation by Sniffer Mouse Behavioural Assays

<jats:p>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.</jats:p>