CTSO and HLA-DQA1 as biomarkers in sepsis-associated ARDS: insights from RNA sequencing and immune infiltration analysis

Abstract

Abstract The onset of sepsis frequently coincides with acute respiratory distress syndrome (ARDS), which constitutes a significant contributor to severe acid–base disturbances in septic patients. In the pathogenesis of sepsis, it conducts a crucial role. lysosomal metabolic disorders and immune imbalance conduct a pivotal role. Despite extensive research into the alterations in immune status during sepsis, few studies have been reported to thoroughly examine the association between lysosomes and sepsis. As a result, this study is predominantly Intended to delve into the link between lysosome-related genes and alterations in the lysosome in the immune microenvironment from the standpoint of bioinformatics in sepsis. The Registration Number was ChiCTR1900021261. Registration Date is 2019/02/04. Method Sepsis data source: Sepsis data was collected from previous clinical data and sequencing results (Originated from BGI Shenzhen Co., Ltd.) and the GO database was utilized for data collection of lysosome-related genes. Differential expression genes (DEGs) were screened on clinical sequencing data by employing IDEP 0.93 software subsequent to quality control. Afterwards, enrichment analysis was conducted by adopting Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co expression Network Analysis (WGCNA), followed by cross referencing of lysosomal genes to identify DEGs associated with lysosomes. GO and KEGG pathway analysis wereperformed subsequently. The genes obtained from PLSGs and WGCNA by Creating a PPI network entails the following steps: the points were intersected at first. Afterwards, CytoHubba and MCODE analysis were performed by utilizing cytoscape software. Next, the intersection was taken to confirm Hub gene sequences, and subsequently the central DEGs tightly associated with existing CTD scores. Notwithstanding the fact that the causes of sepsis are multifaceted, ARDS can often trigger the development of sepsis in numerous cases. Simultaneously, with an aim to predict transcription factor levels in the central nervous system, Cytoscape software was adopted DEGs and to find relevant target miRNAs in the miRWalk database, and a correlated regulatory network was established accordingly. The SEPSIS immune infiltration model was constructed by employing ImmuCellAI software. Afterwards, the association between DEGs and immune microenvironment abundance was constructed by adopting Spearman's method. Last but not least, it is worth noting that single-cell sequencing has been validated as a method to analyze hub gene expression in immune cells of sepsis patients, enabling the selection of key genes that are closely associated with predictive outcomes. Result When acute respiratory distress syndrome (ARDS) is present, the differentially expressed genes (DEGs) are implicated in lysosomal metabolism and the regulation of the immune microenvironment. Six hub DEGs were bound up with sepsis or was attributable to the examinations. On top of that, it was determined that the patients had acute respiratory distress syndrome. The associated immune analysis illustrated a remarkable augment in T cell infiltration in the immune microenvironment of sepsis, while the infiltration relative to DC was reduced at certain level. Positive correlations were found between the two by employing Spearman analysis between hub DEGs and the regulatory role of immune cells. Moreover, it was universally acknowledged that anti-inflammatory immune cells were responsible for the negative correlation. On the basis of single-cell sequencing, it has been determined that CTSO and HLA-DQA1 were expressed in immune cells in sepsis. Aside from that, the survival-death curve direction suggested that they could be utilized as core genes for predicting sepsis-related prognosis analysis. Conclusion An analysis of this study demonstrates the interaction between sepsis lysosome-related metabolism and changes by understanding the pathogenesis of immune cells in the microenvironment. On this basis, we can develop new clinical diagnostics and therapeutic approaches of sepsis and identifying drug targets. Nonetheless, ARDS and sepsis can differ simply by the difference in site of infection; as the etiology of numerous ARDS cases is quite complex, progression to sepsis can occur if infection exacerbates or other complications arise, meeting the diagnostic criteria of sepsis 3.0.

Keywords

• Sepsis
• Acute respiratory distress syndrome
• Immune microenvironment
• Immune infiltration