Plasma Proteomic Signatures for Diverticulitis Risk Stratification

Introduction
Approaches for risk stratification in diverticulitis have emphasized lifestyle factors, with a possible emerging role for molecular signatures. We aimed to evaluate whether plasma proteomic profiles complement dietary and genetic factors in diverticulitis risk stratification.
Materials and methods
This UK Biobank study derived a plasma proteomic risk score for severe diverticulitis (operative or recurrent inpatient disease). The cohort was split into a training set for derivation and an independent testing set for evaluation. Differential expression and gene set enrichment analysis identified pathway-level differences, while least absolute shrinkage and selector operator models calculated the score. To evaluate utility in stratification, the proteomic risk score was included in Cox regression models with demographics, lifestyle factors, and genetic risk. A phenome-wide association study explored for conditions associated with diverticulitis proteomic signatures.
Results
Among 43,539 patients and 1459 plasma proteins measured at enrollment, there were 551 cases of severe diverticulitis throughout follow-up. Differential expression analysis implicated extracellular matrix and neuronal pathways, while least absolute shrinkage and selector operator regression retained 151 proteins. This proteomic risk score was associated with greater risk of severe diverticulitis (hazard ratio [95% confidence interval], 1.48 [1.18-1.87]), and a full model with proteomic and genetic factors improved upon a base model with demographic and lifestyle factors (maximum at 5-y area under the receiver operating characteristics curve [95% confidence interval], training set: 0.83 [0.79-0.86] versus 0.69 [0.64-0.73]; testing set 0.75 versus 0.70; P < 0.01) In the phenome-wide association study, elevated proteomic risk for diverticulitis was associated with renal dysfunction and cardiometabolic traits.ConclusionsPlasma proteomic profiles complemented genetic and lifestyle factors in diverticulitis risk stratification.