Identification of potential serum biomarkers of acute paraquat poisoning in humans using an iTRAQ quantitative proteomic

Abstract

Paraquat (PQ) poisoning has high mortality rates in many countries. Due to it readily being absorbed through the gastrointestinal tract and rapidly excreted in the urine, few biomarkers possess satisfactory specificity and sensitivity in diagnostic and forensic practices. To investigate serum biomarkers in patients with PQ poisoning, pooled sera was analyzed using a proteomic approach based on iTRAQ coupled LC-MS/MS. Of the 413 proteins identified with high confidence, 81 were found to be differentially expressed (1.5-fold change) in the sera of patients with PQ poisoning. The differential expression pattern of 4 of these proteins was validated by enzyme-linked immunosorbent assay (ELISA) in clinical samples. A sera sample from a PQ poisoning patient has shown relatively increased abundance of S100A8 and S100A9. The overexpression of S100A8 and S100A9 was further validated in the lung tissue of PQ-treated rat associated with lung damage. Meanwhile, we identified another two down-expressed proteins, transferrin receptor protein 1 (TfR1) and serum amyloid P-component (SAP), which may be also practicable in human clinical samples as PQ poisoning serum biomarkers. Furthermore, receiver operating characteristic curve analysis confirmed that the expression levels of S100 alarmins, TfR1 and SAP in patient serum could provide a discriminatory diagnostic test for predicting PQ poisoning in patients. Therefore, our results suggest that increased serum levels of S100 alarmins and decreased serum levels of TfR1 and SAP may constitute potential biomarkers for the prediction of PQ poisoning in humans, and might be novel therapeutic targets in PQ poisoning.