Identification of serum peptide biomarkers for cholangiocarcinoma diagnosis and staging via MALDI-TOF MS and LC-MS/MS
A partir de l'analyse, au moyen de technologies de chromatographie liquide et de spectrométrie de masse, d'échantillons sériques prélevés sur 50 témoins sains, 53 patients avec maladie bénigne des voies biliaires, 138 patients atteints d'un cholangiocarcinome et 65 patients atteints d'un carcinome hépatocellulaire, cette étude identifie des biomarqueurs peptidiques pour distinguer ces maladies et déterminer le stade d'un cholangiocarcinome ou d'un carcinome hépatocellulaire
Background : Cholangiocarcinoma (CCA) is a highly aggressive malignancy frequently diagnosed at advanced stages due to the lack of effective biomarkers for early-stage detection. This study aimed to identify serum peptide biomarkers capable of distinguishing healthy individuals, benign bile duct disease, different stages of CCA, and hepatocellular carcinoma (HCC).
Methods : We analyzed 306 serum samples, comprising 50 healthy controls, 53 benign bile duct disease, 138 CCA, and 65 HCC patients. Peptide mass fingerprints (PMFs) were generated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and a random forest model was applied to classify these groups based on PMF patterns. To complement this analysis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on pooled serum samples to identify representative peptides associated with each group.
Results : The 94 PMFs from MALDI-TOF MS yielded high classification performance within the study cohort, with an internal accuracy of 97.96. LC-MS/MS analysis of pooled samples identified representative peptides associated with each disease group, providing complementary information to PMF-based classification. Importantly, peptide biomarkers with high classification performance were associated with specific patient groups.
Conclusion : These findings suggest that serum peptide biomarkers may serve as potential signatures to support CCA diagnosis, staging, and risk stratification, offering a non-invasive approach that warrants further investigation.
British Journal of Cancer , résumé, 2025