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Prognostic evidence also mixes cell-free mtDNA with cellular blood-derived mtDNA, which are not analytically equivalent, while non-malignant injury and inflammation may raise circulating mtDNA and reduce specificity. Following PRISMA 2020, 31 cancer studies (8334 patients) and 1286 controls were synthesized using random-effects models for diagnostic indices and hazard ratios.",{"@graph":69,"@context":125},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/circulating-mitochondrial-dna-measures-across-malignancies-diagnostic-accuracy-and-prognostic-associations/363954/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/circulating-mitochondrial-dna-measures-across-malignancies-diagnostic-accuracy-and-prognostic-associations/363954.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117,121],{"name":108,"@type":109,"acceptedAnswer":110},"Why is circulating mitochondrial DNA considered a liquid-biopsy biomarker?","Question",{"text":111,"@type":112},"It has a high copy number and is released during cellular stress, making it a candidate measurable marker in blood.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How were diagnostic and prognostic evidence synthesized in the study?",{"text":116,"@type":112},"Diagnostic analyses pooled indices mainly from cell-free mtDNA assays, while prognostic analyses pooled circulating or blood-derived mtDNA measures, using random-effects models across 31 studies.",{"name":118,"@type":109,"acceptedAnswer":119},"What did the pooled diagnostic performance show for predominantly cell-free mtDNA assays?",{"text":120,"@type":112},"Sensitivity was 0.73 and specificity 0.80, with a diagnostic odds ratio of 15.41 and an AUC of 0.845, along with substantial heterogeneity between studies.",{"name":122,"@type":109,"acceptedAnswer":123},"Do the authors recommend stand-alone clinical use of circulating mtDNA measures?",{"text":124,"@type":112},"No. The evidence shows diagnostic and prognostic associations, but heterogeneity in pre-analytical handling, assay definitions, and control selection means current evidence does not support stand-alone clinical use.","https://schema.org",{"og:url":83,"og:type":127,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":129,"canonical":83},"index,follow",{"doc_id":131,"site_id":62},363954,1790198308,{"code":4,"msg":5,"data":134},{"doc_id":131,"user_id":135,"nickname":92,"user_avatar":136,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":137,"file_id":138,"file_url":139,"file_type":140,"file_size":141,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":142,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":143,"faqs":144,"seo_title":145,"seo_description":67,"update_tm":146,"read_time":31},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Cancer Medicine  \n|  RESEARCH ARTICLE  OPEN ACCESS \u003Cbr>Circulating Mitochondrial DNA Measures Across Malignancies: Diagnostic Accuracy and Prognostic Associations\u003Cbr>Ziying Zhang1  | Ying Jiang1 | Yu Gong2 | Hui Xie3 | Yaqian Han1  | Peng Chen4 \u003Cbr>1Department of Radiation Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China | 2School of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China | 3Department 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 | 4Department of Diagnostic Radiology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China\u003Cbr>Correspondence: Yaqian Han ([hanyaqian@hnca.org.cn](hanyaqian@hnca.org.cn)) | Peng Chen ([chenpeng@hnca.org.cn](chenpeng@hnca.org.cn))\u003Cbr>Received: 31 March 2026 | Revised: 27 June 2026 | Accepted: 16 July 2026\u003Cbr>Keywords: cell-free mitochondrial DNA | circulating mitochondrial DNA | diagnostic accuracy | liquid biopsy | prognosis |\n| --- |\n| ABSTRACT\u003Cbr>Background: Circulating 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.\u003Cbr>Methods: Following 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) .\u003Cbr>Results: Predominantly 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 |\n|  |\n| Abbreviations: APL, acute promyelocytic leukemia; AUC, area under the curve; BCa, bladder cancer; BD, benign disease; cf-mtDNA, cell-free mitochondrial DNA; cf-nDNA, cell-free nuclear DNA; CI, confidence interval; CIR, cumulative incidence of relapse; CNKI, China National Knowledge Infrastructure; COPD, chronic obstructive pulmonary disease; CRC, colorectal cancer; CTC, circulating tumor cell; ctDNA, circulating tumor DNA; ddPCR, droplet digital PCR; DFS, disease-free survival; DOR, diagnostic odds ratio; EC, endometrial cancer; EOC, epithelial ovarian cancer; EWS, Ewing's sarcoma; FN, false negative; FP, false positive; GC, gastric cancer; HCC, hepatocellular carcinoma; HNC, head and neck cancer; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; HS, healthy subject; MDS, myelodysplastic syndrome; MT-CYB, mitochondrially encoded cytochrome b; mtDNA, mitochondrial DNA; mtDNA-79, a 79-bp mitochondrial 16S-rRNA fragment; NLR, negative likelihood ratio; NOS, Newcastle-Ottawa Scale; NSCLC, non-small cell lung cancer; OS, overall survival; PCa, prostate cancer; PFS, progression-free survival; PLR, positive likelihood ratio; PTC, papillary thyroid cancer; qPCR, quantitative real-time PCR; QUADAS-2, revised Quality Assessment of Diagnostic Accurac","cbCailinJfRcr2s9","https://ap.wps.com/l/cbCailinJfRcr2s9","pdf",7614013,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"Why is circulating mitochondrial DNA considered a liquid-biopsy biomarker?\",\"answer\":\"It has a high copy number and is released during cellular stress, making it a candidate measurable marker in blood.\"},{\"question\":\"How were diagnostic and prognostic evidence synthesized in the study?\",\"answer\":\"Diagnostic analyses pooled indices mainly from cell-free mtDNA assays, while prognostic analyses pooled circulating or blood-derived mtDNA measures, using random-effects models across 31 studies.\"},{\"question\":\"What did the pooled diagnostic performance show for predominantly cell-free mtDNA assays?\",\"answer\":\"Sensitivity was 0.73 and specificity 0.80, with a diagnostic odds ratio of 15.41 and an AUC of 0.845, along with substantial heterogeneity between studies.\"},{\"question\":\"Do the authors recommend stand-alone clinical use of circulating mtDNA measures?\",\"answer\":\"No. The evidence shows diagnostic and prognostic associations, but heterogeneity in pre-analytical handling, assay definitions, and control selection means current evidence does not support stand-alone clinical use.\"}]","Circulating Mitochondrial DNA Measures Across Malignancies - Diagnostic Accuracy and Prognostic Associations | PDF",1790154478]