Serum Olink proteomics-based exploration of novel predictive biomarkers for necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal emergency in preterm infants, yet reliable serum candidates for presymptomatic risk stratification remain lacking. In this exploratory study, serial pre-diagnostic serum samples from a prospective discovery cohort were profiled using the Olink proteomics platform. NEC cases and controls were individually matched for gestational age, birth weight, and sampling time. Top-ranked proteins were assessed via enzyme-linked immunosorbent assay in an independent validation cohort and examined in surgical intestinal tissues. Fibroblast growth factor 5 (FGF5) showed the highest discriminative performance with an area under the receiver operating characteristic curve of 0.848. Lower circulating FGF5 levels were reproduced in the validation cohort, although the apparently perfect discrimination was imprecise because of the small sample size. Intestinal FGF5 expression was also reduced in NEC specimens. These findings support FGF5 as a promising exploratory biomarker for early NEC risk assessment, warranting larger multicenter validation and mechanistic investigation.