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

Abstract

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of the neoplasms develop, and is non-invasively collected. Hence, this work aimed to unveil alterations in the urinary volatile profile of patients diagnosed with BC compared with cancer-free individuals, as well as differences among patients diagnosed at different tumor stages, to identify candidate biomarkers for non-invasive BC diagnosis and staging. Urine analysis was performed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results unveiled that BC patients have a distinct urinary volatile profile characterized by higher levels of several alkanes and aromatic compounds, and lower levels of aldehydes, ketones and monoterpenes. Seventeen significantly altered volatiles were used to evaluate the performance for overall BC detection, disclosing 70% sensitivity, 89% specificity and 80% accuracy. Moreover, distinct urinary volatile profiles were found among patients diagnosed at different tumor stages (Ta/Tis, T1 and ≥T2). This work identified distinct urinary volatile signatures of BC patients with potential for non-invasive detection and staging of bladder cancer.

Bladder cancer biomarker screening based on non-targeted urine metabolomics

“…S5), and the results showed that the correlation between age, gender, and BMI and the 27 differential metabolites were small (|r|≤0.3). Thus, it can be concluded that age, gender, and BMI in this study did not show a signi cant correlation with the changes in metabolites detected between bladder cancer patients and the cancer-free controls [3].…”

“…Currently, screening for bladder cancer still relies heavily on invasive cystoscopy [2], which can directly show tumor lesions in the bladder, and can perform biopsies for further pathological examination. However, this uncomfortable procedure can lead to urethral injury, urinary tract infection, and hematuria [3]. On the other hand, urine cytology is a non-invasive method to detect cancer cells in urine.…”

A Panel of Bile Volatile Organic Compounds Servers as a Potential Diagnostic Biomarker for Gallbladder Cancer

“…Therefore, this may explain why the levels of (E)-hept-2-enal, (E)-2-hexenal, (E)-2-pentenal, (E)-2-octenal, and hexanal are reduced in the bile of tumor patients. These findings were consistent with some studies that volatile aldehydes are decreased in tumor cells ( 36 , 37 ).…”

Machine Learning in Prediction of Bladder Cancer on Clinical Laboratory Data

“…Urine ketone is one of the routine urinalysis. Only a few studies reported an alteration of ketone in patients with bladder cancer in a metabolomics study [ 71 ]. However, ketone body in urine has been considered as a high correlation to diabetes [ 72 ].…”