Testing for novel stool-based protein biomarkers improves CRC screening

Mass spectrometry testing for novel protein biomarkers in stool outperformed testing for hemoglobin in detecting colorectal cancer and advanced adenomas, according to data published in Annals of Internal Medicine.

“Like hemoglobin in [fecal immunochemical test], protein biomarkers can be translated into simple and cost-effective antibody-based screening tests. However, thus far, alternative protein biomarkers have failed to improve current hemoglobin-based [colorectal cancer] stool-screening tests,” Linda J.W. Bosch, PhD, from Netherlands Cancer Institute in Amsterdam, and colleagues wrote. “Technologic advancements in mass spectrometry now allow for in-depth proteomics for biomarker discovery in complex biological samples. Discovering biomarkers directly in the biological sample taken for screening, namely stool, may be a powerful alternative.”

Although using fecal immunochemical tests (FITs) to identify hemoglobin is commonly used for noninvasive colorectal cancer screening, its sensitivity is lacking, according to researchers. Bosch and colleagues conducted a case-control study to identify novel protein biomarkers in stool that complement or perform better than hemoglobin in detecting CRC and advanced adenomas.

Using mass spectrometry, they analyzed 315 stool samples from one series of 12 patients with colorectal cancer and 10 patients without colorectal neoplasia (control), and a second series of 81 patients with colorectal cancer, 40 patients with advanced adenomas, 43 with nonadvanced adenomas and 129 without colorectal neoplasia. In addition, they examined 72 FIT samples from a third independent series of 14 patients with colorectal cancer, 16 with advanced adenomas, 18 with nonadvanced adenomas and 24 without colorectal neoplasia.

Overall, 834 human proteins were identified and 29 proteins showed statistically significant abundance in colorectal cancer compared with control stool samples in both series. Four protein combinations reached sensitivities of 80% and 45% for identifying colorectal cancer and advanced adenomas, respectively, at 95% specificity, which was more sensitive than that of hemoglobin alone. Several proteins could be measured in small sample volumes used in FIT-based screening programs and could be distinguished between colorectal cancer and control samples (P < .001).

“The current study presents novel stool-based protein biomarkers with a higher discriminatory power than hemoglobin for detecting [colorectal cancer] and advanced adenomas, as well as proteins that, when combined with hemoglobin, may improve detection of [colorectal cancer] and advanced adenomas,” Bosch and colleagues wrote. “Supported by proof of concept that these proteins can be detected in small FIT samples; these biomarkers have the potential to improve current FIT-based [colorectal cancer] screening.” – by Savannah Demko

Disclosures: Bosch is an inventor of a biomarker with a patent pending. Please see the study for all other authors’ relevant financial disclosures.