SRS153 - Serum Raman spectroscopy and correlation with metabolomic profiles in colorectal surveillance for Lynch syndrome

Abstract Objectives Lynch syndrome (LS) mutation carriers face an elevated risk of colorectal cancer (CRC) and undergo surveillance colonoscopy, a procedure associated with risk and burden. Raman spectroscopy (RS), which provides biochemical fingerprints of biological samples, may offer a complementary diagnostic approach. A prior pilot study at our institution suggested biochemical differences between LS-associated and sporadic CRC. This study compared the circulating metabolome of LS individuals (carriers, polyp, CRC) with sporadic counterparts to identify distinct metabolites and correlate them with RS peaks. Methods Serum samples from LS-CRC (n = 9), LS-polyp (n = 10), and LS-carrier (n = 20) groups were analysed using RS, Gas Chromatography–Mass Spectrometry (GCMS), and Matrix-Assisted Laser Desorption Ionisation–Time of Flight (MALDI-TOF). LS-CRC cases were site- and stage-matched with sporadic CRC, including BRAF-mutant tumours. LS-polyp samples were matched by size, subtype, and dysplasia grade, and LS-carriers were age- and sex-matched to controls. Results GCMS principal components analysis revealed clear separation between CRC, polyp, and control samples (P = 0.001). MALDI-TOF showed clustering of controls, though CRC and polyp groups overlapped. CRC cases displayed elevated phenylalanine, L-isoleucine, L-serine, L-ornithine, and threonine, with reduced short-chain fatty acids. PCA showed no clear distinction between LS-CRC and sporadic CRC, but hierarchical clustering separated LS-CRC and BRAF-mutant CRC from non-BRAF CRC. LS-polyp and LS-carrier groups also demonstrated subtle differences. Conclusions LS individuals display metabolomic profiles distinct from non-LS controls. Further work will link metabolite changes to RS peaks.