In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

• MeSH
• ceramidy * krev   MeSH
• hmotnostní spektrometrie metody   MeSH
• kalibrace MeSH
• laboratoře * normy   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• referenční standardy * MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ceramidy * MeSH

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.

• MeSH
• antigen CA-19-9 krev   MeSH
• ceramidy krev   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• lysofosfatidylcholiny krev   MeSH
• metabolismus lipidů genetika   MeSH
• multivariační analýza MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory slinivky břišní krev   diagnóza   mortalita   patologie   MeSH
• proporcionální rizikové modely MeSH
• senzitivita a specificita MeSH
• sfingomyeliny krev   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CA-19-9 MeSH
• ceramidy MeSH
• lysofosfatidylcholiny MeSH
• nádorové biomarkery MeSH
• sfingomyeliny MeSH