Cell-Free Mitochondrial DNA as a Novel biomarker for stress-related conditions - Meta-Analysis

Abstract

Mitochondria is a central organelle that regulates various physiological functions of the cell, like Reactive oxygen species (ROS) generation, apoptosis, and energy metabolism; its dysfunction due to various stress factors will result in compromised O2 regulation, mitochondrial-related diseases and other conditions. Few studies have shown that Circulating cell-free mitochondrial DNA(CFmt-DNA) content in body fluids will change many stress, environmental and exercise needs. In this study, we aim to understand the relationship between CFmt-DNA and various stress conditions like Alzheimer's disease, Acute Appendicitis, strenuous exercise, major depressive disorder etc. This meta-analysis is done by PRISMA standards, and a specified methodology was used to conduct the study. We looked for relevant studies up to August 2022 in PubMed, Web of Science, and Science direct ELSEVIER. Meta Mar web tool was used to analyse the data. Additionally, research on publication bias was also done. After the initial search, a total of 832 articles were identified. Six articles were chosen for our meta-analysis after filtering out meta-analyses or reviews (165 publications), erroneous data (591 publications) and studies that lacked access to raw data (73 publications). Data from six studies were combined to compare the normalised CFmt-DNA copy numbers between the experimental group under various stress conditions and the control group. The copy number of CFmt-DNA did not differ significantly in comparison between the control and the experimental; the Standardized Mean Difference (SMD) was −1.38 (95% CI, −3.56 to 0.79), P = 0.1699 (P > 0.05) in the random effect model. The results of the random effects analysis showed that the study has heterogeneity in the research (I2 = 96%, P < 0.01). In the subgroup analysis, the sample collected from Cerebrospinal fluid (CSF), Tissue and Ex vivo lung perfusion (EVLPP) were statistically significant (P < 0.05). In conclusion, CFmt-DNA can be used as a potential biomarker even if there are variations in copy number. The copy number of CFmt-DNA is influenced by the stress situation and the biological source of the sample.