Exploratory Serum-Based Surface-Enhanced Raman Spectroscopy Analysis in Crohn's Disease: A Pilot Cross-Sectional Study.

Crohn's disease (CD) is a chronic inflammatory bowel disease requiring accurate and timely diagnosis. Current diagnostic tools may be invasive, costly, or insufficiently specific. Surface-enhanced Raman spectroscopy may enable rapid, minimally invasive detection of disease-associated biochemical alterations in serum. This cross-sectional pilot study included age- and sex-matched patients with Crohn's disease and healthy controls. Serum samples were analyzed using surface-enhanced Raman spectroscopy. Spectral data were preprocessed and analyzed using principal component analysis-linear discriminant analysis and partial least squares-discriminant analysis. Classification performance was evaluated using leave-one-out cross-validation. Variable importance in projection scores was used to identify discriminatory vibrational bands. Fifty-four participants fulfilled the clinical inclusion criteria, while 51 participant-level spectra were retained for final classification analysis. PCA-LDA differentiated CD from healthy controls with a sensitivity of 85.19%, specificity of 91.67%, accuracy of 88.24%, and AUC of 0.881. PLS-DA showed slightly higher performance, with a sensitivity of 88.89%, specificity of 95.83%, accuracy of 92.16%, and AUC of 0.937. Relevant discriminatory bands were observed at 498, 639, 728, 813, 1136, 1205, 1443, 1579, and 1657 cm