Exploration of serum biomarkers associated with pathological changes in acute respiratory distress syndrome lung tissues through transcriptomics and proteomics sequencing
Objective To explore serum protein biomarkers that align with the pathological protein changes in lung tissues of pulmonary acute respiratory distress syndrome(ARDS).Methods A total of 40 healthy SPF-grade C57BL/6 mice were divided into two groups according to the random number table method:a control group(Control group,n=19)and an ARDS experimental group[lipo-polysaccharide(LPS)group,n=21].The LPS group was administered with LPS through intratracheal injection,while the Control group received an equal volume of saline through intratracheal injection.Twenty-four hours after modeling,mice in both groups were eutha-nized under anesthesia.Lung tissues were collected for hematoxylin-eosin(H-E)staining and wet/dry(W/D)analysis to evaluate the ARDS model.In addition,lung tissues from the Control and LPS groups were collected for transcriptomic and proteomic sequencing.Se-rum samples from both groups were also subjected to proteomic analysis.These sequencing results were then integrated with previous proteomic data from serum and lung tissues of coronavirus disease 2019(COVID-19)induced ARDS patients obtained by the research team,in an effort to identify serum protein biomarkers consistent with the pathological protein changes in lung tissues.Results Compared with the Control group,the LPS group showed increases in pathological injury scores in lung tissues and pulmonary W/D(all P<0.05),and the ARDS model of mice was successfully constructed.A total of 28 common differentially expressed proteins(CM-DEP)were identified through transcriptomic and proteomic analysis of lung tissues,along with proteomic sequencing of serum.These proteins exhibited consistent trends in both lung tissues and serum of ARDS mice.Further analysis incorporating proteomic data from lung tis-sues and plasma of ARDS patients identified four candidate proteins,namely haptoglobin(HP),S100 calcium-binding protein A9(S100A9),serum amyloid A1(SAA1),and serum amyloid A2(SAA2).These proteins showed a positive correlation with the severity of ARDS in patients Conclusions The four candidate proteins(HP,S100A9,SAA1,and SAA2)have the potential to serve as serum biomarkers reflecting pathological changes in ARDS lung tissues and may hold significant clinical value.