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UH researcher reports efficient tests that may replace endoscopy in the future

Jason Martinez

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HOUSTON, TX — In two published journal articles, a University of Houston biomedical researcher reported an advancement in diagnosing intestinal diseases; including colorectal cancer, ulcerative colitis and Crohn’s disease using stool proteins.

The current gold standard for colon cancer testing measures blood (hemoglobin) present in stool, and tests for inflammatory bowel disease (IBD) measure levels of calprotectin—a protein that detects inflammation in the intestines.

Chandra Mohan, Hugh Roy and Lillie Cranz Cullen, Endowed Professors of biomedical engineering in the UH Cullen College of Engineering, said, “The unique aspect of both research reports is that we are looking at stool samples comprehensively, and not just at one or two favorite molecules. We are casting a wide net, and this has never been done before.”

For colon cancer, typical fecal blood tests seek hemoglobin in stool samples. Hemoglobin is only one of more than a thousand proteins being hunted in Mohan’s work.

In “Nature Communications”—a peer-reviewed, open access, scientific journal published by Nature Research since 2010—Mohan reported, “By the time you see blood, it might be too late, and there are other proteins that appear in the stool if someone has colon cancer, and they may appear much earlier than when the blood appears.”

Utilizing aptamer-based screening, Mohan and team screened 1,317 proteins looking for precursor biomarkers of colon cancer and found five elevated.

Aptamers are pieces of DNA that can be chosen to bind to other molecules. They work as a bait, carefully selected for each protein they will try to detect. If the protein is present in the stool, it will bind to the aptamer in the library. And if it’s not present, it will be washed away.

“Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of colorectal cancer,” said Mohan.

Mohan’s research team includes Robert S. Bresalier from University of Texas MD Anderson Cancer Center, Nicholas Chia from Mayo Clinic and Hao Li and Kamala Vanarsa from University of Houston.

Mohan reported similar findings in the Journal of Gastroenterology, in early diagnosis of ulcerative colitis and Crohn's disease. He found several proteins elevated in pediatric patients with the disease after screening for 1,300 proteins. Mohan’s team took samples from patients at four different time periods, providing the researchers a rare view into disease progression.

"Using the new biomarkers, we can predict if the disease will become worse or if the intestines will become more inflamed. Stool proteins assayed at baseline can predict how the disease might progress in the weeks and months ahead,” said Mohan.

The IBD study represented the first use of the aptamer-based screen of stool samples in IBD, and represented the largest-ever targeted stool proteomic study 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, fecal calprotectin,” said Mohan.

He hopes to replace the invasive endoscopy test by discovering stool markers that can predict what is occuring in the intestine without having to do endoscopy. Stool tests for proteins can be done at home and through the mail.

In 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.

For more details and updates, visit the University of Houston's website at https://uh.edu/.

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