Analysis of bulk RNA-seq data from sepsis patients reveals sepsis-associated lncRNAs and targeted cell death-related genes contributing to immune microenvironment regulation

Yanwei Cheng; Lijun Xu; Jiaoyang Wang; Xue Cao; Dong Chen; Peirong Zhang; Lei Yang; Lijie Qin

doi:10.3389/fimmu.2023.1026086

Analysis of bulk RNA-seq data from sepsis patients reveals sepsis-associated lncRNAs and targeted cell death-related genes contributing to immune microenvironment regulation

Front Immunol. 2023 Feb 2:14:1026086. doi: 10.3389/fimmu.2023.1026086. eCollection 2023.

Authors

Yanwei Cheng¹, Lijun Xu¹, Jiaoyang Wang¹, Xue Cao², Dong Chen³, Peirong Zhang¹, Lei Yang¹, Lijie Qin¹

Affiliations

¹ Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
² Department of Rheumatology and Immunology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
³ Wuhan Ruixing Biotechnology Co., Ltd, Wuhan, China.

Abstract

Background: Sepsis is a life-threatening organ dysfunction syndrome that leads to the massive death of immune cells. Long non-coding RNAs (lncRNAs) have been reported to exert key regulatory roles in cells. However, it is unclear how lncRNAs regulate the survival of immune cells in the occurrence and development of sepsis.

Methods: In this study, we used blood whole transcriptome sequencing data (RNA-seq) from normal controls (Hlty) and patients with uncomplicated infection (Inf1 P), sepsis (Seps P), and septic shock (Shock P), to investigate the fraction changes of immune cell types, expression pattern of cell death-related genes, as well as differentially expressed lncRNAs. Association network among these factors was constructed to screen out essential immune cell types, lncRNAs and their potential targets. Finally, the expression of lncRNAs and cell death genes in sepsis patients were validated by qRT-PCR.

Results: In this study, we found fifteen immune cell types showed significant fraction difference between Hlty and three patient groups. The expression pattern of cell death-related genes was also dysregulated in Hlty compared with patient groups. Co-expression network analysis identified a key turquoise module that was associated with the fraction changes of immune cells. We then identified differentially expressed lncRNAs and their potential targets that were tightly associated with the immune cell dysregulation in sepsis. Seven lncRNAs, including LINC00861, LINC01278, RARA-AS1, RP11-156P1.3, RP11-264B17.3, RP11-284N8.3 and XLOC_011309, as well as their co-expressed cell death genes, were finally identified, and we validated two lncRNAs (LINC00861 and LINC01278) and four mRNA targets using qRT-PCR in sepsis samples.

Conclusion: The global analysis of cell death-related genes in the occurrence and development of sepsis was carried out for the first time, and its expression regulation mode was displayed. The expression pattern of sepsis-associated lncRNAs were analyzed and identified, and the lncRNAs were significantly related to the change of immune cell proportion. We highlight the important roles of lncRNAs and their potential targets in the regulation of immune cell fraction changes during sepsis progression. The identified lncRNAs and their target genes may become new biomarkers and therapeutic targets of sepsis.

Keywords: cell death genes; co-expression network; immune cells; lncRNAs; sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Death
Exome Sequencing
Gene Regulatory Networks
Humans
RNA, Long Noncoding* / genetics
RNA-Seq
Sepsis*

Substances

RNA, Long Noncoding

Grants and funding

The present work was supported by the 23456 Talent Project of Henan Provincial People’s Hospital to LQ and LY, Research Startup fund of Henan Provincial People’s Hospital to YC and XC, and Henan Province Medical Science and Technology Co-construction Project to YC (LHGJ20220028).