title: MALDI imaging-based classification of hepatocellular carcinoma and non-malignant lesions in fibrotic liver tissue.
abstract: Histopathologic differentiation of nodular lesions in cirrhotic liver is difficult even for experienced hepatopathologists especially regarding diagnosis of hepatocellular carcinoma (HCC) in biopsies. For this reason, new tissue markers are needed to reinforce histopathologic decision-making. With advances in molecular techniques, proteomic analysis may help to confirm the diagnosis of HCC. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful technology which allows to determine and to localize proteins directly in tissue sections. Using MALDI IMS proteomic patterns of cryosections with lesions of HCC (n = 15) and non-malignant fibrotic liver tissue (n = 11) were investigated to establish a classification model of HCC, which was validated in an independent set of tissue to distinguish HCC (n = 10) from regenerative nodules (n = 8). By correlating generated mass spectrometric images with the histology of the tissue sections we found that the expression of 4 proteins as indicated by m/z 6274, m/z 6647, m/z 6222 and m/z 6853 was significantly higher in HCC tissue than in non-tumorous liver tissue. The generated classification model based on the most significant 3 differentially expressed proteins allowed a reliable prediction of benign and malignant lesions in fibrotic liver tissue with a sensitivity and specificity of 90 % in the validation set. The identified MALDI IMS proteomic signature can be diagnostically helpful to allow simplifying the diagnostic process and minimize the risks of delays in establishing the objective final diagnosis and initiating treatment of patients with HCC.
authors.affiliation: Department of InternaI Medicine IV, Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Jena.
authors.forename: C
authors.initials: C
authors.lastname: Marquardt
authors.affiliation: Department of InternaI Medicine IV, Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Jena.
authors.forename: T
authors.initials: T
authors.lastname: Tolstik
authors.affiliation: Department of InternaI Medicine IV, Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Jena.
authors.forename: C
authors.initials: C
authors.lastname: Bielecki
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena.
authors.forename: R
authors.initials: R
authors.lastname: Kaufmann
authors.affiliation: Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University Jena.
authors.forename: A C
authors.initials: AC
authors.lastname: Crecelius
authors.affiliation: Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University Jena.
authors.forename: U S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena.
authors.forename: U
authors.initials: U
authors.lastname: Settmacher
authors.affiliation: Department of InternaI Medicine IV, Gastroenterology, Hepatology and Infectious Diseases, Jena University Hospital, Jena.
authors.forename: A
authors.initials: A
authors.lastname: Stallmach
authors.affiliation: Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena.
authors.forename: O
authors.initials: O
authors.lastname: Dirsch
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009363:Neoplasm Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins