In a recent study, a biomedical researcher at the University of Houston discovered a breakthrough in diagnosing intestinal diseases such as ulcerative colitis, colorectal cancer, and Crohn’s disease using stool proteins. The Journal of Gastroenterology and Nature Communications both published these findings.
The current gold standard for colon cancer testing is to look for blood (haemoglobin) in stool, while tests for inflammatory bowel disease (IBD) look for calprotectin levels, a protein that detects intestinal inflammation.
“What distinguishes both research reports is that we examined stool samples holistically, rather than focusing exclusively on one or two preferred molecules,” said Chandra Mohan, Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering at the University of Houston Cullen College of Engineering.
“We’re casting a broad net, which has never been done before,” Mohan added.
Typical faecal blood tests for colon cancer look for haemoglobin in stool samples. Haemoglobin is just one of over a thousand proteins being hunted in Mohan’s work.
“By the time you see blood, it may be too late, and there are other proteins that appear in the stool of people who have colon cancer that may appear much earlier than the blood,” Mohan reported in Nature Communications.
Mohan and colleagues screened 1,317 proteins for precursor biomarkers of colon cancer using aptamer-based screening and identified five that were elevated. Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin all emerged as promising colorectal cancer biomarkers, outperforming stool haemoglobin.
Aptamers are DNA fragments that can be selected for their ability to bind to other molecules. They act as bait, having been carefully chosen for each protein they will attempt to detect. If the protein is detected in the stool, it will bind to the library’s aptamer. Without the protein, it will be washed away.
“Longitudinal studies are necessary to determine the clinical utility of these novel biomarkers in the early detection of colorectal cancer,” Mohan explained.
Robert S. Bresalier of the University of Texas MD Anderson Cancer Center; Nicholas Chia of the Mayo Clinic; and Hao Li and Kamala Vanarsa of the University of Houston comprised Mohan’s research team.
Predicting the future using IBD markers
Mohan reported similar findings in the Journal of Gastroenterology, where he discovered several proteins were elevated in paediatric patients with ulcerative colitis and Crohn’s disease after screening for 1300 proteins.
Ferritin, Fibrinogen, Haptoglobin, Haemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are all significantly increased in ulcerative colitis and Crohn’s disease, respectively.
The researchers collected samples from patients at four distinct time points, providing a unique window into disease progression.
“We can predict whether the disease will worsen or the intestines will become more inflamed using the new biomarkers. At baseline, stool proteins can be used to forecast how the disease will progress in the coming weeks and months “Mohan stated.
The IBD study is the first to employ an aptamer-based screen of stool samples in IBD, and it is also the largest targeted stool proteomic study ever conducted in IBD.
“We demonstrate the utility of comprehensive aptamer-based proteomic screens in identifying novel disease biomarkers for IBD that outperform the current gold standard, faecal calprotectin,” said Mohan.
Mohan’s hope is to replace the invasive endoscopy test by finding stool markers that can predict what is happening in the intestine without having to do an endoscopy. Stool protein tests can be performed at home or via mail.
On this paper, Mohan was joined by Subra Kugathasan from Emory University whose lab supplied the stool samples; Suresh Venkateswaran, Emory University; Sanam Soomro and Kamala Vanarsa, University of Houston.
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