A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers

Abstract

Our group recently developed a urinary 6-biomarker panel for the diagnosis of prostate cancer (PCa) which has a higher level of accuracy compared to the serum prostate specific antigen (PSA) test. Herein, urine from an independent cohort of PCa patients and cancer-free controls was analyzed to further validate the discriminative power of that panel. Additionally, urine from patients diagnosed with bladder cancer (BC) and renal cancer (RC) were included to evaluate the site-specificity of the panel. Results confirmed the ability of the 6-biomarker panel to discriminate PCa patients from controls, but not from other urological cancers. To overcome this limitation, an untargeted approach was performed to unveil discriminant metabolites among the three cancer types. A 10-biomarker panel comprising the original panel plus four new metabolites was established to discriminate PCa from controls, BC, and RC, with 76% sensitivity, 90% specificity, and 92% accuracy. This improved panel also disclosed better accuracy than serum PSA test and provides the basis for a new non-invasive early detection tool for PCa.

Discovery of Volatile Biomarkers for Bladder Cancer Detection and Staging through Urine Metabolomics

“…The decrease in hexanal and 2-methylbutanal levels may be attributed to oxidation by aldehyde dehydrogenase (ALDH) to yield carboxylic acids or a decrease in aldehyde formation through lipid peroxidation [ 14 ]. Hexanal has also been found decreased in urine of patients diagnosed with other cancer types (e.g., colorectal cancer, prostate cancer, leukemia and lymphoma) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], whereas 2-methylbutanal was found decreased in patients diagnosed with head and neck cancer [ 37 ]. The presence of formaldehyde in human body can be associated with several sources, such as folate derivatives breakdown, protein and nucleic acid demethylation, glycine and serine metabolism or exogenous sources (e.g., smoking and diet) [ 13 ].…”

“…The decrease in 4-heptanone levels corroborate a previous study performed in urine of BC patients [ 11 ]. Moreover, 2-butanone and 4-heptanone have been found altered in other cancer types but the direction of the variation differed among studies [ 31 , 32 , 37 , 39 , 43 , 44 , 45 , 46 ]. Finally, lower levels of two monoterpenes (carvone and piperitone) were observed in urine of BC patients.…”

Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

“…The volatilomic studies have been more focused in the definition of biomarker panels for possible detection through biosensors rather than proposing individual biomarkers [ 93 , 99 , 103 ]. The smallest biomarker panel reported included four metabolites (2,6-dimethyl-7-octen-2-ol, 3-octanone, 2-octanone and pentanal) [ 93 ], which unveiled accuracies at least equal to PSA (accu.…”

“…of 63–65% for the 4-biomarker panel [ 7 , 93 ]. Remarkably, a 6-biomarker panel (hexanal, 2,5-dimethylbenzaldehyde, 4-methylhexan-3-one, dihydroedulan IA, methylglyoxal, 3-phenylpropionaldehyde) [ 99 ] and an improved 10-biomarker panel (methylglyoxal, hexanal, 3-phenylpropionaldehyde, 4-methylhexan-3-one, 2.5-dimethylbenzaldehyde, dihydroedulan IA, ethylbenzene, heptan-2-one, heptan-3-one, 4-(2-methylpropoxy)butan-2-one, methyl benzoate, 3-Methylbenzaldehyde) [ 103 ] were recently proposed that outperformed PSA in all performance parameters (PSA: acc = 62–75%, sens = 20.5%, spec = 51–91% [ 4 , 7 , 8 ]; 6-biomarker panel: acc = 86%, sens = 89%, spec = 83% [ 99 ]; 10-biomarker panel: acc = 92%, sens = 76%, spec = 90% [ 103 ]). Notably, the 10-biomarker panel proved to be able to differentiate PCa from cancer-free individuals as well as from other urological cancers (renal and bladder cancers) [ 103 ].…”

Tracking the Progression of Triple Negative Mammary Tumors over Time by Chemometric Analysis of Urinary Volatile Organic Compounds

“…Furthermore, VOCs can be noninvasively sampled and detected in human biofluids including sweat, saliva, blood, breath and urine. Groups have previously identified VOC biomarkers for lung [ 15 ], prostate [ 16 , 17 , 18 , 19 ] and breast cancer [ 20 ], even classifying unique cancers from each other [ 21 , 22 ].…”