Abstract
BackgroundThis study aimed to assess the correlation of long noncoding (lnc) RNA intersectin (ITSN) 1‐2 expression with disease risk, severity, inflammation, and survival in sepsis patients.MethodsThree hundred and nine intensive care unit (ICU)‐treated sepsis patients and 300 healthy controls were consecutively recruited in this study. Blood samples were collected from all sepsis patients within 24 hours after admitted to ICU and from healthy controls at the time of health screening, and the expression of lncRNA ITSN1‐2 in plasma was detected by quantitative polymerase chain reaction. Disease severity was assessed by physicians using acute physiology and chronic health evaluation (APACHE) II score on day 1 after ICU admission. Additionally, the plasma inflammatory cytokines (including tumor necrosis factor α (TNF‐α), interleukin 1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17) were measured by enzyme‐linked immunosorbent assay (ELISA) kits.ResultslncRNA ITSN1‐2 was highly expressed in sepsis patients compared to healthy controls and could differentiate sepsis patients from healthy controls with area under the curve (AUC) 0.777 (95% CI: 0.740‐0.813). lncRNA ITSN1‐2 expression was positively correlated with APACHE II score, C‐reactive protein (CRP), TNF‐α, IL‐6, and IL‐8 levels, but negatively correlated with IL‐10 level. In addition, lncRNA ITSN1‐2 was highly expressed in non‐survivors compared to survivors and could distinguish survivors from non‐survivors in sepsis patients with AUC 0.654 (95% CI: 0.581‐0.726).ConclusionCirculating lncRNA ITSN1‐2 is upregulated, and its high expression associates with increased disease severity and inflammation as well as poor prognosis in sepsis patients.
Highlights
Sepsis, characterized as severe systemic inflammation, is defined as life‐threatening organ dysfunction caused by a dysregulated host response to infection, which is a global disease burden with rising incidence and severity, especially in developing countries.[1,2] As in China, the incidence of sepsis is up to 37.3% and the mortality of sepsis ranges from 33.5% to 48.7% in intensive care unit (ICU) set‐ ting patients, and its mortality is approximately onefold higher than the rates among developed countries.[3-6]
Accumulating studies have revealed that multiple lncRNAs are implicated in acute inflammatory response against microbial infection through transcriptionally regu‐ lating inflammatory gene expression.[7] lncRNA intersectin (ITSN) 1‐2 is one of lncRNA family members located in chromosome 21 with its NONCODE gene ID NONHSAG032726.2, and its length was 451 bp with NONCODE transcript ID NONHSAT081856.2, starting from 33976355 to end site 33976982.8 It is reported that lncRNA ITSN1‐2 high expression is correlated with increased disease risk and activity as well as inflammation degree of rheumatoid arthritis (RA).[8]
Considering that RA and sepsis are both characterized as system‐ atic inflammatory response and the latter presents with even more severe inflammation, and our preliminary research in a small popu‐ lation observed that lncRNA ITSN1‐2 was extremely upregulated in sepsis patients, we speculated that lncRNA ITSN1‐2 may be involved in the development and progression of sepsis
Summary
Sepsis, characterized as severe systemic inflammation, is defined as life‐threatening organ dysfunction caused by a dysregulated host response to infection, which is a global disease burden with rising incidence and severity, especially in developing countries.[1,2] As in China, the incidence of sepsis is up to 37.3% and the mortality of sepsis ranges from 33.5% to 48.7% in intensive care unit (ICU) set‐ ting patients, and its mortality is approximately onefold higher than the rates among developed countries.[3-6]. The objective of this study was to assess whether lncRNA ITSN1‐2 could distinguish sepsis from healthy controls, and its correlation with disease sever‐ ity, inflammation, and survival in sepsis patients. This study aimed to assess the correlation of long noncoding (lnc) RNA intersectin (ITSN) 1‐2 expression with disease risk, severity, inflammation, and sur‐ vival in sepsis patients. Blood samples were collected from all sepsis patients within 24 hours after admitted to ICU and from healthy controls at the time of health screening, and the expression of lncRNA ITSN1‐2 in plasma was detected by quantitative polymerase chain reaction. Conclusion: Circulating lncRNA ITSN1‐2 is upregulated, and its high expression as‐ sociates with increased disease severity and inflammation as well as poor prognosis in sepsis patients
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