Evidence map›Paper›PMID 42538597›Full record

ArticleCancer medicine2026

Circulating Mitochondrial DNA Measures Across Malignancies: Diagnostic Accuracy and Prognostic Associations.

Ziying Zhang, Ying Jiang, Yu Gong, Hui Xie, Yaqian Han, Peng Chen

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Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Ziying ZhangDepartment of Radiation Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.ORCID https://orcid.org/0000-0002-7402-7893
Ying JiangDepartment of Radiation Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
Yu GongSchool of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China.
Hui XieDepartment of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Yaqian HanDepartment of Radiation Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.ORCID https://orcid.org/0000-0002-6716-4320
Peng ChenDepartment of Diagnostic Radiology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.ORCID https://orcid.org/0009-0003-1949-9411

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCirculating mitochondrial DNA is being investigated as a liquid-biopsy biomarker because of its high copy number and release during cellular stress. However, diagnostic estimates vary across tumor types and assays, and prognostic studies have measured both cell-free mtDNA and cellular blood-derived mtDNA, which are not analytically equivalent. Non-malignant tissue injury and inflammation may also increase circulating mtDNA, limiting disease specificity.

methodsFollowing PRISMA 2020 guidance, seven databases were searched through December 2025. Diagnostic analyses synthesized predominantly cell-free mtDNA assays, whereas prognostic analyses synthesized the circulating or blood-derived mtDNA measures reported by the original studies. Random-effects models were used to pool diagnostic indices and hazard ratios across 31 unique studies comprising 8334 patients with cancer and 1286 controls. The protocol was registered in PROSPERO (CRD420261301732).

resultsPredominantly cell-free mtDNA assays showed a pooled sensitivity of 0.73, specificity of 0.80, diagnostic odds ratio of 15.41, and area under the summary receiver operating characteristic curve of 0.845, with substantial between-study heterogeneity. The mtDNA-79 subgroup showed a sensitivity of 0.79, specificity of 0.93, and area under the curve of 0.909. Higher circulating or blood-derived mtDNA measures were associated with poorer overall survival (HR = 1.70, 95% CI: 1.42-2.03) and relapse-free survival (HR = 2.04, 95% CI: 1.71-2.44), but not with progression-free survival or mortality. MT-CYB-based measures showed a stronger adverse prognostic association than MT-ND1-based measures.

conclusionsCirculating mtDNA measures show diagnostic and prognostic associations across malignancies, but current evidence does not support stand-alone clinical use. Heterogeneity in specimen matrix, pre-analytical handling, assay definition, and disease-control selection requires standardized multicenter validation. mtDNA-79 and MT-CYB warrant further study, while total mtDNA abundance should be interpreted as a cancer-associated rather than cancer-specific signal unless combined with tumor-informed genomic or fragmentomic features.

Indexed as

Biomarkers, TumorCell-Free Nucleic AcidsDNA, MitochondrialNeoplasmsHumansLiquid BiopsyPrognosisBiomarkers, TumorCell-Free Nucleic AcidsDNA, Mitochondrialcell‐free mitochondrial DNAcirculating mitochondrial DNAdiagnostic accuracyliquid biopsyprognosis

Identifiers

PMID42538597
PMCPMC13428033

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