Development and Validation of a Highly Sensitive Urine-Based Test to Identify Patients with Colonic Adenomatous Polyps

Abstract

Objectives:Adenomatous polyps are precursors of colorectal cancer; their detection and removal is the goal of colon cancer screening programs. However, fecal-based methods identify patients with adenomatous polyps with low levels of sensitivity. The aim or this study was to develop a highly accurate, prototypic, proof-of-concept, spot urine-based diagnostic test using metabolomic technology to distinguish persons with adenomatous polyps from those without polyps.Methods:Prospective urine and stool samples were collected from 876 participants undergoing colonoscopy examination in a colon cancer screening program, from April 2008 to October 2009 at the University of Alberta. Colonoscopy reference standard identified 633 participants with no colonic polyps and 243 with colonic adenomatous polyps. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to define a diagnostic metabolomic profile for colonic adenomas. A urine metabolomic diagnostic test for colonic adenomatous polyps was established using 67% of the samples (un-blinded training set) and validated using the other 33% of the samples (blinded testing set). The urine metabolomic diagnostic test's specificity and sensitivity were compared with those of fecal-based tests.Results:Using a two-component, orthogonal, partial least-squares model of the metabolomic profile, the un-blinded training set identified patients with colonic adenomatous polyps with 88.9% sensitivity and 50.2% specificity. Validation using the blinded testing set confirmed sensitivity and specificity values of 82.7% and 51.2%, respectively. Sensitivities of fecal-based tests to identify colonic adenomas ranged from 2.5 to 11.9%.Conclusions:We describe a proof-of-concept spot urine-based metabolomic diagnostic test that identifies patients with colonic adenomatous polyps with a greater level of sensitivity (83%) than fecal-based tests.

Clinical validation of a novel urine-based metabolomic test for the detection of colonic polyps on Chinese population

“…Comparison of the urine-based metabolomics test with commercially available fecal-based tests The sensitivities and specificities for three fecal-based are also summarized in Table 1 [6]. When the specificity was set similar as the fecalbased tests at 95.6%, PolypDx™ China 2 outperformed the fecal-based tests in sensitivity (19.1 vs. 2.5-11.9%, respectively) for colonic adenoma detection.…”

“…No dietary or activity modification was required before the urine collection. Samples were stored at 4°C within 4 h and then frozen at −80°C within 24 h. Colonoscopy was performed within 1 week after the urine collections as described elsewhere [6].…”

“…A diagnostic test for the detection of adenomatous polyps was established using the concentration of the identified key metabolites in urine along with key clinical information (e.g., age, sex, smoking history). With colonoscopy results as the gold standard, the urine metabolomic diagnostic test was able to detect colonic adenomatous polyps with a sensitivity of 88.9%, a specificity of 50.2%, and area under curve (AUC) of 0.752 [6]. Metabolomic Technologies Inc. (MTI) has brought the urine metabolomic diagnostic test, PolypDx™, to clinical use in North America.…”

“…The research group of Dr. Richard Fedorak has developed a metabolomic-based urine test for the detection of adenomatous polyps through the metabolic profiling of 876 urine samples at the University of Alberta (Edmonton, Alberta, Canada) [6]. A diagnostic test for the detection of adenomatous polyps was established using the concentration of the identified key metabolites in urine along with key clinical information (e.g., age, sex, smoking history).…”

Emerging methods in colorectal cancer screening

“…Detection of increased metabolite levels (acetate, lactate, serine, sarcosine, asparagine, dimethylspermine, betaine or choline) represents another emerging detection method for early‐stage colorectal cancer. A study published in 2014 reported a metabolomics‐based urine spot test capable of colonic adenoma detection with a greater level of sensitivity (83 per cent) than FIT, suggesting that more cancer metabolite biomarkers may be on the way.…”