Plasma Lipidomic Fingerprinting to Distinguish among Hepatitis C-related Hepatocellular Carcinoma, Liver Cirrhosis, and Chronic Hepatitis C using MALDI-TOF Mass Spectrometry: a Pilot Study

download Full Article (PDF file)

Ana Maria Passos-Castilho1, Edson Lo Turco2, Maria Lúcia Ferraz3, Carla Matos3, Ivonete Silva3, Edison Parise3, Eduardo Pilau4,5, Fabio Gozzo4, Celso Granato1

1) Department of Medicine;
2) Department of Surgery;
3) Department of Gastroenterology, Federal University of Sao Paulo, Sao Paulo, SP
4) Chemistry Institute, University of Campinas, Campinas, SP
5) Department of Chemistry, University of Maringa, Maringa, PR, Brazil



Background & Aims: Hepatitis C (HC) is a major cause of hepatocellular carcinoma (HCC), and a late diagnosis is the main factor for the poor survival of patients. There is an urgent need for identifying sensitive and specific biomarkers for HCC diagnosis. In the present study, plasma lipid patterns of patients with HC-HCC, HC-liver cirrhosis (LC), and chronic HC (CHC) were assessed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).

Methods. Plasma samples of 25 patients with HC-HCC, 15 patients with HC-LC, and 25 patients with CHC were evaluated by MALDI-MS using a Q-ToF premier (Synapt) mass spectrometer (Waters, Manchester, UK) equipped with a 200-Hz solid-state laser in the mass range between m/z (mass-to-charge ratio) of 700-1200.

Results. A total of 2205 ions were initially obtained and 7 ions (m/z) were highlighted as corresponding to the most important lipids to differentiate HCC patients from LC and CHC patients. The specific lipidomic expression signature generated resulted in an overall predictive accuracy of 93% of HC-HCC and HC-LC, and 100% of HC-HCC and CHC. The 7-peak algorithm distinguished HCC from LC with a sensitivity of 96% and a specificity of 87%, and HCC from CHC with both sensitivity and specificity of 100%.

Conclusion. MALDI-MS-specific signature peaks accurately distinguished patients with HC-HCC from those with HC-LC and CHC. The results indicate the potential of MALDI-MS and the selected peaks to improve HCC surveillance in patients with viral C cirrhosis and chronic hepatitis C.

Key words: hepatocellular carcinoma - hepatitis C - lipidomics - fingerprints - lipids - MALDI-MS.