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Clinical Trial
. 2019 Feb 22;14(2):e0212808.
doi: 10.1371/journal.pone.0212808. eCollection 2019.

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition

Yi Yang  1   2 , Jingjuan Yang  2 , Biying Yu  2 , Li Li  2 , Lin Luo  2 , Fengfeng Wu  1 , Binbin Wu  1
Affiliations
Clinical Trial

Association between circulating mononuclear cell mitochondrial DNA copy number and in-hospital mortality in septic patients: A prospective observational study based on the Sepsis-3 definition

Yi Yang et al. PLoS One. .

Abstract

Purpose: To explore the association between circulating mononuclear cell mitochondrial DNA copy number and the prognosis of sepsis patients based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3 definition).

Methods: A total of 200 adult patients who had recently devoloped sepsis were prospectively recruited as the study cohort. Demographic and clinical data were recorded along with a 28-day outcome. Mononuclear cell mtDNA copy number was assessed by quantitative PCR.

Results: The 28-day outcome of sepsis patients was significantly associated with circulating mononuclear cell mtDNA copy number. The median mononuclear cell relative mtDNA copy number of survivors was significantly higher than that of nonsurvivors (406.68, range 196.65-625.35 vs. 320.57, range 175.98-437.33, p = 0.001). The Cox proportional hazard survival model analysis indicated that mononuclear cell relative mtDNA copy number was significantly negative associated with the 28-day outcome. For every additional unit of mononuclear cell mtDNA relative copy number, the risk of death falls by 0.1% (HR = 0.999, 95% CI = 0.998 to 1.000, p = 0.017).

Conclusions: Our data indicate first that circulating mononuclear cellular mtDNA copy number might be helpful for outcome predictions in sepsis patients, and second that lower mtDNA copy number implied poor prognosis.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Representative standard curve and amplification plot from patient samples.
(A) NADH dehydrogenase 1 complementary DNA was serially (1:10) diluted to prepare a series of standards (mtDNA standard) with known DNA copy number. The assay was linear over the range (325.195–3251950 copies) of DNA copy numbers (R2 = 0.9986). The amplification plot shows no irregular amplification for the standard diluents. (B) Beta ACTIN complementary DNA was serially (1:10) diluted to prepare a series of calibrators (nDNA standard) with known DNA copy number. The assay was linear over the range (255.487–2554870 copies) of DNA copy numbers (R2 = 0.9998). The amplification plot shows no irregular amplification for the standard diluents.
Fig 2
Fig 2. Box plots of the relative amount of mononuclear cell mtDNA copy number between survivors and nonsurvivors.
The survivors had median mononuclear cell mtDNA copy number of 406.68. The median mononuclear cell mtDNA copy number for nonsurvivors was significantly lower at 320.57 (p = 0.001).
Fig 3
Fig 3. Kaplan–Meier analysis.
Compared with high mononuclear mtDNA copy number, those with low mtDNA copy number had a higher rate of 28-day mortality (p<0.05).
See this image and copyright information in PMC

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