Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs.

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Colorectal cancer (CRC) screening using fecal hemoglobin immunodetection (FIT) and endoscopy reduces mortality but faces participation challenges.
• False positives in FIT screening can lead to unnecessary procedures and patient anxiety.
• Soluble-CD26 (sCD26), linked to immune function and inflammation, and its enzyme activity (DPP4) were investigated for their potential in improving CRC screening accuracy.

Purpose of the Study:

• To evaluate the utility of sCD26 and DPP4 activity in reducing false positives in colorectal cancer (CRC) screening.
• To assess the correlation of sCD26 and DPP4 activity with CRC and advanced adenomas.
• To propose a sequential testing strategy combining FIT with blood biomarkers.

Main Methods:

• A cohort of 1703 individuals undergoing colonoscopy provided serum samples for sCD26 and DPP4 activity analysis.
• Serum biomarkers were analyzed for differences based on sex, age, and colonoscopy findings (advanced adenomas, CRC).
• FIT results from 918 participants were compared with biomarker data, focusing on false positive rates.

Main Results:

• sCD26 and DPP4 activity showed significant differences based on sex and age.
• Both sCD26 and DPP4 activity progressively decreased in individuals with advanced adenomas and CRC.
• A combined biomarker strategy (sCD26, DPP4, and their ratio) identified nearly all advanced adenomas and CRC cases while halving false positives compared to FIT alone.

Conclusions:

• sCD26 and DPP4 activity are potential biomarkers for improving the specificity of colorectal cancer (CRC) screening.
• A sequential approach combining FIT with blood biomarker testing (sCD26/DPP4) may enhance screening efficiency and reduce unnecessary colonoscopies.
• Further validation of this combined biomarker strategy is warranted for clinical implementation.