AUTHOR=Fan Jiajie , Shi Shanshan , Qiu Yunxiang , Liu Mingnan , Shu Qiang TITLE=Analysis of signature genes and association with immune cells infiltration in pediatric septic shock JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1056750 DOI=10.3389/fimmu.2022.1056750 ISSN=1664-3224 ABSTRACT=Background

Early diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in pediatric septic shock.

Methods

We screened a dataset of children with septic shock from the GEO database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WCGNA) was used to screen the key modules. Least absolute shrinkage and selection operator (LASSO) and random forest analysis were finally applied to identify the signature genes. Then gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. And the immune cells infiltration was subsequently classified via using CIBERSORT.

Results

A total of 534 DEGs were screened from GSE26440. The data then was clustered into 17 modules via WGCNA, which MEgrey module was significantly related to pediatric septic shock (cor=−0.62, p<0.0001). LASSO and random forest algorithms were applied to select the signature genes, containing UPP1, S100A9, KIF1B, S100A12, SLC26A8. The receiver operating characteristic curve (ROC) of these signature genes was 0.965, 0.977, 0.984, 0.991 and 0.989, respectively, which were verified in the external dataset from GSE13904. GSEA analysis showed these signature genes involve in positively correlated fructose and mannose metabolism and starch and sucrose metabolism signaling pathway. CIBERSORT suggested these signature genes may participate in immune cells infiltration.

Conclusion

UPP1, S100A9, KIF1B, S100A12, SLC26A8 emerge remarkable diagnostic performance in pediatric septic shock and involved in immune cells infiltration.