Circulating mitochondrial DNA as a biomarker in critically ill patients: A meta-analysis and trial sequential analysis / 解放军医学杂志

ABSTRACT

Objective To systematically review the association between circulating cell-free mitochondrial DNA (mtDNA) and prognosis in critically ill patients by using Meta-analysis and trial sequential analysis (TSA). Methods The PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang Data were searched from creating of the database up to October, 2018 for cross-sectional studies, case-control studies, or cohort studies on the relevance between mtDNA and prognosis in critically ill patients. Then, Meta-analysis and TSA were performed using Stata 12.0 software and TSA v0.9 software. Results A total of 15 prospective cohort studies involves 1318 patients. The results of Meta-analysis showed that mtDNA was associated with prognosis in critically ill patients (SMD=1.08, 95%CI 0.66-1.49, P=0.000). Subgroup analysis of mitochondrial DNA specific primer, centrifugal parameters, source of mitochondrial DNA as mtDNA standard curve, types of sample, extraction technology, types of outcome and disease, and age showed that, except for the types of the sample, outcome and disease, and age, results were affected apparently and differently by the rest factors. Sensitivity analysis indicated that the model is stable and reliable. Egger test revealed there were maybe publication bias. And the results of TSA displayed that all of the cumulative Z-curve strode traditional threshold value and TSA threshold value which suggested that affirmative conclusions had been reached, namely mtDNA could predict the prognosis of serious diseases as its biomarker clearly. Conclusions Current evidence suggests that mtDNA in circulation could be considered as a biomarker for the prognosis of severe disease. However, due to possible publication bias, the above conclusions should be treated with caution and it also requires a standard process to extract mtDNA from peripheral blood and more trials to prove it.