Biomarkers Of Radiation Pneumonia Based On Serum Proteomic

ObjectiveReliable biomarkers are needed to more accurately predict radiation pneumonitis(RP).This experiment adopts non-small cell lung cancer patients serum samples as the research object,through proteomic quantitative analysis,the differences in protein expression of patients with pneumonia and non-pneumonia after radiotherapy at different time points(0,3,and 6 weeks)was screened.MethodsFrom October 2017 to July 2018,28 patients with locally advanced non-small cell lung cancer received radiation therapy in our hospital.Serum samples were respectively taken pre-radiotherapy,3rd week and 6th week of radiotherapy.Finally,3patients developed grade ≥2 radiation pneumonitis and their serums was the experimental group.From the other 25 patients,the serum of patients with the same sex,same pathological type,similar age and clinical stage as the experimental group were selected as the control group.Differentially expressed proteins were identified using TMT labeling quantification and liquid chromatography-mass spectrometry,and analyzed by relevant bioinformatics analysis methods.ResultsBy mass spectrometry of peptides,there were 812 quantifiable proteins.Bioinformatics analysis further revealed that these proteins are mainly involved in binding,biological regulation,metabolic processes,signaling processes,and pertussis signaling pathways in KEGG.Using 1.2 times as the threshold for differential expression change and statistical t-test p <0.05 as the significance threshold,we found that ZYX and FETUB expression were up-regulated in the pre-radiotherapy group and the 3rd week of radiotherapy group.CSTA and CALML5 were down-regulated in the pre-radiotherapy group and the 6th week of radiotherapy group.NNT was significantly down-regulated in all these three groups,the ratios were 0.296,0.314,0.238.Moreover,NNT,HPR,and PZP in the pre-radiotherapy group were significantly down-regulated,also the most prominent down-regulation of all differential proteins in the three groups.The protein interaction network map was retrieved from the STRING database,and it was found that FETUB interacts with PZP between these differential proteins,and PZP has a certain correlation with the pathophysiological pathways of radiation pneumonia reported so far,such as TGF-β、IL-1β、 IL-6、TNF and inflammatory response related pathways.ConclusionProteomics showed that there were differentially expressed proteins in the presence and absence of radiation pneumonitis at diferrent time of radiotherapy.Based on the proteomic analysis method and protein interaction network diagram,we found that FETUB and PZP are the best candidate proteins related to radiation pneumonitis,which can provide the basis for the next step to verify and predict the biomarkers of radiation pneumonitis.