Serie, Daniel

22 Background: Glycosylation plays a pivotal role in host immune response during cancer development. Recently, we have reported specific changes in blood-based glycoforms for the early detection of advanced adenomas (AAs) and colorectal cancer (CRC). This study aims to identify glycoproteomic biomarkers associated with various polyp types, as glycosylation abnormalities are linked to neoplastic transformation, and CRC risk varies by polyp histology. Methods: Samples from an observational study (NCT05445570) were used to identify three distinct histologic polyp groups: adenomatous (AP), hyperplastic (HP), or serrated (SP). Combining liquid-chromatography/mass-spectrometry and artificial-intelligence powered data processing, our glycoproteomic profiling platform assessed glycopeptide (GP) and non-glycosylated peptide quantification transitions from the serum samples. We used multi-nominal response logit models to examine the relationship between polyp types and biomarkers. An a priori biomarker panel was interjected as exposures in the model. Each marker is assessed independently for inclusion into our final model. The final model utilized biomarkers found to have a significant association with the presence of AP, SP, or HPs along with age, sex, and BMI. Results: We identified 1,035 subjects with distinct polyp histologies and 1,300 polyp-free controls. We found a significant increase in relative risk (RR) for polyp presence in patients who were: >60 years (AP RR 1.40), male (AP RR 1.74), or had a BMI> 25. From the GP biomarker panel, 15 GPs were associated with risk of polyp presence; however, only 7 GP markers were significantly associated after adjusting for age, sex, and BMI. Two biomarkers were found to have a protective effect for the risk of an adenomatous polyp (RR 0.37; RR 0.39). Three biomarkers increased the risk of an adenomatous polyp (RR 1.31; RR 1.42; RR 1.98). One biomarker was found to increase the risk of a hyperplastic polyp (RR 1.42). Two biomarkers were found to increase the risk of serrated polyps (RR 1.67; RR 2.08) and one biomarker was found to decrease the risk of serrated polyps (RR 0.77). Conclusions: This is a novel exploratory study using GP biomarkers as it relates to risk of polyp presence by distinct histology. The use of these biomarkers allows us to harness the power of glycobiology in the liquid biopsy domain for AAs/CRC detection. The exact function of these GP markers during the development of different polyp types needs to be further explored through future studies.