Commentary: Why have different key biomarkers been reported in the same types of samples from patients with identical diseases?

Accurate biomarkers are crucial for early disease detection and improved prognosis. However, the inconsistent reporting of different key biomarkers in the same types of samples from patients with identical diseases in biomarker discovery studies is often questioned. In contrast to such instrumental analyses, the murine olfactory system consistently distinguishes subtle variations in genetically determined individual-unique body odors in urine samples and more pronounced differences in diet-modulated and fluctuating body odors. Interestingly, sniffer mouse behavioral assays revealed that prostate and bladder cancers alter olfactory cues in urine samples to be more intense compared with diet-modulated or genetically determined individual-specific body odors. The causes of inconsistent key biomarkers include high inter-individual and inter-sample variability due to diet-induced metabolites and cosmetic or environmental contaminations. Previously, we proposed experimental procedures tolerant to such noise-like variability or fluctuation, leading to the identification of ten urinary volatile biomarkers for prostate cancer, including 2,6-di(propan-2-yl)phenol as a unique biomarker for bladder cancer. This commentary discusses the theoretical basis of urinary volatile biomarkers and future directions for complementary biomarker development for diagnosis.