Plasma Proteomic Signatures for Diverticulitis Risk Stratification.

Area of Science:

• Gastroenterology
• Proteomics
• Genetics

Background:

• Diverticulitis risk stratification traditionally relies on lifestyle factors.
• Emerging evidence suggests a role for molecular signatures in predicting diverticulitis risk.

Purpose of the Study:

• To evaluate if plasma proteomic profiles can augment dietary and genetic factors for diverticulitis risk stratification.
• To develop and validate a plasma proteomic risk score for severe diverticulitis.

Main Methods:

• A UK Biobank cohort was used, with a training set for score derivation and a testing set for validation.
• Differential expression and pathway analysis identified key proteins and pathways.
• Least absolute shrinkage and selector operator regression models calculated the proteomic risk score.
• Cox regression models assessed the score's utility alongside demographic, lifestyle, and genetic factors.

Main Results:

• A proteomic risk score derived from 151 proteins was associated with an increased risk of severe diverticulitis (HR 1.48).
• Integrating proteomic and genetic factors significantly improved risk prediction models compared to demographic and lifestyle factors alone.
• Phenome-wide association studies linked elevated proteomic risk to renal dysfunction and cardiometabolic traits.

Conclusions:

• Plasma proteomic profiles offer valuable complementary information for diverticulitis risk stratification.
• The developed proteomic risk score, combined with genetic and lifestyle data, enhances the prediction of severe diverticulitis.
• These findings suggest potential for novel diagnostic and management strategies in diverticulitis.