Stool-based protein biomarkers could improve colorectal cancer screening

Reuters Health Information: Stool-based protein biomarkers could improve colorectal cancer screening

Stool-based protein biomarkers could improve colorectal cancer screening

Last Updated: 2017-11-22

By Will Boggs MD

NEW YORK (Reuters Health) - Several stool-based protein biomarkers are more sensitive than the fecal immunochemical test (FIT) for detecting colorectal cancer (CRC) and advanced adenomas, researchers report.

"The finding of the current study brings a new biomarker test within reach that will allow detection (of) substantially more advanced adenomas and cancers without increasing the number of false-positive test results, and will allow more of these lesions to be removed endoscopically than by surgery," Dr. Gerrit A. Meijer from Netherlands Cancer Institute, in Amsterdam, told Reuters Health by email.

FIT, which has largely replaced the guaiac-based fecal occult blood test for CRC screening, is only 79% sensitive for detecting CRC and 31% sensitive for finding advanced colonic adenomas.

Dr. Meijer and colleagues sought to identify proteins in stool that outperform or complement fecal hemoglobin as a biomarker for early detection of CRC and advanced adenomas. Their findings were published online November 21 in Annals of Internal Medicine.

They focused on hemoglobin subunit alpha 1 (HBA1) and six proteins with significantly higher sensitivity than HBA1: complement C3, alpha-2-macroglobulin, haptoglobin, complement C5, fibronectin 1, and ceruloplasmin.

Ten different panels, each containing four proteins, had substantially higher accuracy (area under the curve, 0.93-0.94) compared with HBA1 alone (AUC, 0.88), as well as statistically significantly higher sensitivity at 95% specificity (65%-80% vs. 43%, respectively).

These panels were consistently more sensitive than HBA1 for detecting CRC or advanced adenoma in a separate series of stool samples from 81 individuals with CRC, 40 with advanced adenoma, 43 with non-advanced adenoma, and 129 without colorectal neoplasia.

An off-the-shelf antibody-based assay, which included four of the proteins earlier found to distinguish CRC from controls in whole-stool samples, showed that three of the proteins were present at significantly greater concentrations in FIT samples from patients with CRC or advanced neoplasia than in samples from controls.

"This has the potential to dramatically increase the impact of stool-based colorectal cancer screening programs," Dr. Meijer said. "Moreover, the new biomarkers can be detected with the same sampling method as used for FIT. Upon further clinical validation, it then would be easy to migrate FIT-based screening programs the new biomarker test. This strengthens the potential for getting this new test actually implemented."

"We currently are conducting the next clinical validation steps and aim to complete this process within the next three years," he said. "We are also already preparing a prospective clinical trial (n=13,500) in the context of the Dutch national colorectal cancer screening program in which the new test will be compared head-to-head to the current FIT test."

Dr. Meijer has patents pending for multiple applications of CRC-related biomarkers, and several of the other authors are inventors of a biomarker with a patent pending.


Ann Intern Med 2017.

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