Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors

Abstract

BackgroundDifferentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry.Material/MethodsIn our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system.ResultsA total of 27 discriminant peaks (p<0.05) in mass spectra of serum samples were found by ClinPro Tools software. Recognition capabilities of the established models were 100% (GA), 89.38% (SNN), and 80.84% (QC); cross-validation rates were 81.67% (GA), 81.11% (SNN), and 86.11% (QC). The accuracy rates of the blinded validation test were 78% (GA), 84% (SNN), and 84% (QC). From the 27 discriminatory peptide peaks analyzed, 3 peaks of m/z 2860.34, 2881.54, and 3155.67 were identified as a fragment of fibrinogen alpha chain, fibrinogen beta chain, and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), respectively.ConclusionsOur results demonstrated that MS technique can be helpful in differentiation of benign and malignant liver tumors. Fibrinogen and ITIH4 might be used as biomarkers for the diagnosis of malignant liver tumors.

MALDI‐TOF‐MS analysis in low molecular weight serum peptidome biomarkers for NSCLC

“…It has oncogenic effects by binding to vascular endothelial growth factor, promoting endothelial cell proliferation, and interacting with stromal proteins by using integrins as a scaffold for cell migration. 17 In previous studies, high levels of fibrinogen α chain fragments were detected in cholangiocarcinoma, 18 hepatocellular carcinoma, 19 and gastric carcinoma. 20 Klupczynska et al 21…”

“…It was indicated that tumor cells can promote blood coagulation by interacting with endothelial cells and platelets, and releasing active substances to activate platelets, resulting in increased fibrinogen levels in the blood of cancer patients. In previous studies, high levels of fibrinogen α chain fragments were detected in cholangiocarcinoma, 18 hepatocellular carcinoma, 19 and gastric carcinoma 20 . Klupczynska et al 21 combined ZipTip technology with MALDI‐TOF‐MS for the first time to study the serum proteome of patients with NSCLC and healthy controls.…”

A Fibrinogen Alpha Fragment Mitigates Chemotherapy-Induced MLL Rearrangements

“…Further reports described increased expression of fibrinogen in a large variety of tumors (57)(58)(59) and correlation of high fibrinogen plasma levels with cancer risk, worse disease-free and poor overall survival (59)(60)(61). Peptides derived from the C-terminus of fibrinogen a (62-64), including a peptide identical to Fa27 (65), were also identified during clinical association studies in search of serumderived tumor biomarkers. Notably, one study focusing on acute myeloid leukemia (AML) showed that a 38 amino acid long Cterminal fragment of fibrinogen a encompassing Fa27 was found to be reduced in sera from newly diagnosed, refractory and relapsed cases and associated with improved overall survival of patients, which was the opposite of what was observed for the fibrinogen a level (62).…”

Serum proteomic predicts effectiveness and reveals potential biomarkers for complications in liver transplant patients

“…MALDI-TOF MS is a valuable tool for the profiling of biological samples with relatively low abundance that is fast, highly sensitive, and has a high throughput [20]. In addition, the use of MALDI-TOF MS combined with magnetic beads is a new method that has been used to identify cancer and other diseases [21][22][23][24][25]. This method is also suitable for detection of serum protein biomarkers in liver transplant patients.…”