Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Abstract

Background The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients’ urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.

Feasibility of Integrating Canine Olfaction with Chemical and Microbial Profiling of Urine to Detect Lethal Prostate Cancer

“…VOCs elevated in the Gleason 9 prostate cancer samples were different from those previously reported [19], including trimethyl silanol, a volatile siloxane resulting from the degradation of silicones. However, our study design (Gleason 9 prostate cancer versus biopsy-negative controls)…”

“…Total raw data is available in the Supporting Information. Similarly to previous studies [19,40], we found individual peaks representing VOCs that were elevated or reduced in prostate cancer versus biopsy-negative control urine samples at p<0.05 (Fig 3B, C).…”

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

“…Preparation of urine samples and analytical conditions followed the protocol described by Lima et al [17]. To detect a large number of volatile compounds, two different analysis procedures based on headspace solid-phase microextraction (HS-SPME) coupled to GC-MS were performed.…”

“…Volatile organic compounds (VOCs) are end products of cellular metabolism, especially promising as potential non-invasive biomarkers for translation into the clinic due to the recent advancements in the development of electronic-nose (e-nose) sensors [16]. In this vein, we have recently reported a urinary biomarker panel for PCa diagnosis comprising six volatile compounds, that outperformed PSA sensitivity and accuracy [17]. Here, we extend our previous work to further validate the biomarker panel in an independent cohort of PCa patients and also to assess the performance of the panel for discriminating PCa from other common urological cancers, namely bladder cancer (BC) and renal cancer (RC).…”

The diagnostic value of RASSF1A promoter methylation in prostate cancer: A systematic review and meta-analysis

“…The early screening of prostate cancer can aid in the early diagnosis and treatment of the disease, ultimately benefitting patients. [40] At present, the main clinical challenge for the diagnosis and treatment of prostate cancer is the lack of reliable biomarkers for the early detection and prognosis monitoring of PCa. [41] Studies have shown that abnormal DNA methylation plays an important role in the development of tumors, leading to the silencing and activation of some tumor suppressor and protective genes.…”