journal article·2025-10Open access

Revealing Cell‐Free Mitochondrial DNA Breakage Patterns as Novel Biomarkers for Sepsis

Haitang Liao, Ruiyan Ma, Shuai Hao, Xuxin Tan, Xue Zeng, Rui Song, Bing Chen, Zhezhe Cao, Wei Shen, Zhenchun Luo, Jianfeng Huang, He Huang, Liangming Liu, Chenyang Duan

Advanced Science· Volume 12· Issue 39

Abstract

Abstract Accurate early diagnosis and prognosis of sepsis remain major clinical challenges. This study explores specific plasma cell‐free mitochondrial DNA (cfmtDNA) breakage patterns as potential biomarkers for sepsis. Plasma samples from ten non‐sepsis control patients and 63 sepsis patients are analyzed using mitochondrial DNA fragmentomics, revealing distinct breakage sites in the RNR2 (positions 2474–2478) and COX2 (positions 7761, 7775, 7776, 7777, and 7783) regions, which are intact in healthy individuals but exhibited high‐frequency breakage in sepsis patients. Diagnostic models based on these breakage sites show superior accuracy for sepsis detection (AUC = 0.865) and prognosis prediction (AUC = 0.809) compared to traditional cfmtDNA copy number assessments. Notably, COX2 breakage frequency correlated with inflammatory markers and SOFA scores, highlighting its prognostic potential. Mechanistic analyses suggest that reduced protein binding in sepsis may increase cfmtDNA susceptibility to cleavage by bacterial restriction endonucleases. These findings indicate that plasma cfmtDNA breakage characteristics can serve as valuable biomarkers for early sepsis detection and therapeutic monitoring.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Mitochondrial Function and Pathology · Metabolomics and Mass Spectrometry Studies · Antibiotic Resistance in Bacteria

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Pinnacle Disciplinary Group (Department of Anesthesiology) The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China

Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis the Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China

Department of Intensive Care Unit Chongqing Hospital of Traditional Chinese Medicine Chongqing 400011 P. R. China

Department of Cardiovascular Surgery Xinqiao Hospital Army Medical University Chongqing 400037 P. R. China

Research Institute of General Surgery Jinling Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210000 P. R. China

Sinotech Genomics Co., Ltd Shanghai 201103 P. R. China

State Key Laboratory of Trauma and Chemical Poisoning Department of Shock and Transfusion Army Medical Center Army Medical University Chongqing 400042 P. R. China

Funding

National Natural Science Foundation of China

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