Investigation of serum proteome homeostasis during radiation therapy by a quantitative proteomics approach

Abstract

The purpose of the present study is to analyze the serum proteome of patients receiving Radiation Therapy (RT) at different stages of their treatment to discovery candidate biomarkers of the radiation-induced skin lesions and the molecular pathways underlying the radiation signatures. Six stages of RT treatment were monitored from patients treated because of brain cancer: before starting the treatment, during the treatment (four time points), and at 4 weeks from the last RT dose. Serum samples were analyzed by a proteomics approach based on the Data Independent Acquisition (DIA) mass spectrometry (MS). RT induced clear changes in the expression levels of 36 serum proteins. Among these, 25 proteins were down- or up-regulated significantly before the emergence of skin lesions. Some of these were still deregulated after the completion of the treatment. Few days before the appearance of the skin lesions, the levels of some proteins involved in the wound healing processes were down-regulated. The pathway analysis indicated that after partial body irradiation, the expression levels of proteins functionally involved in the acute inflammatory and immune response, lipoprotein process and blood coagulation, were deregulated.

Radiation Therapy in Patients With Brain Cancer: Post-proteomics Interpretation

“…The serum proteome profile of early-stage treatment with radiation of brain cancer subjects was assessed for the bioinformatics. 4 The list of DE proteins one week after treatment of RT in serum is listed in Table 1. The bioinformatics approach is the PPI network analysis of differentially expressed proteins of patients' serum with the early stage (one week after therapy) prior to the skin lesion.…”

“…The patients (male and female) were a mixture of different tumor types to reduce the chance of background interference. 4 Fifteen significant proteins in RT-treated serums were identified by the main study 1 week after exposure. 4 These proteins were chosen for PPI network analysis by the application of Cytoscape 3.7.2 and its integrated plug-ins.…”

“…4 Fifteen significant proteins in RT-treated serums were identified by the main study 1 week after exposure. 4 These proteins were chosen for PPI network analysis by the application of Cytoscape 3.7.2 and its integrated plug-ins. 11 A network was constructed via the protein query from the STING database source in Cytoscape.…”

“…The serum is one of the appropriate sources to investigate the molecular level changes. 4 In this way, the potential biomarkers of any condition could be revealed by promising large-scale studies. 5 Moreover, proteomics is a novel molecular investigation for discovering the biomarkers of a specific state.…”

“…Depending on therapy intensity and duration, the proteome quality could change. 4 Additional information about biomarkers introduced by a proteomics study of these conditions is feasible by bioinformatics such as protein-protein interaction (PPI) network analysis. 7 A DEP that has centrality values in a PPI network could be more promising as a biomarker since its changes could cause a vast range of malfunctions in a system of protein interactions.…”