Liquid Biopsies Based on Cell-Free DNA Integrity as a Biomarker for Cancer Diagnosis: A Meta-Analysis

Author:

Rodríguez-Ces Ana María123ORCID,Rapado-González Óscar12345ORCID,Salgado-Barreira Ángel678,Santos María Arminda9,Aroso Carlos9ORCID,Vinhas Ana Sofia9ORCID,López-López Rafael2410ORCID,Suárez-Cunqueiro María Mercedes12410ORCID

Affiliation:

1. Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain

2. Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain

3. Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain

4. Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain

5. Cancer Biology & Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal

6. Department of Public Health, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

7. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiology and Public Health—CIBERESP), 28029 Madrid, Spain

8. Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain

9. UNIPRO-Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, 4585-116 Gandra, Portugal

10. Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS, SERGAS), 15706 Santiago de Compostela, Spain

Abstract

Liquid biopsies have been identified as a viable source of cancer biomarkers. We aim to evaluate the diagnostic accuracy of cell-free DNA integrity (cfDI) in liquid biopsies for cancer. A comprehensive literature search was conducted through PubMed, Embase, Web of Science, and Cochrane Library up to June 2024. Seventy-two study units from forty-six studies, comprising 4286 cancer patients, were identified and evaluated. The Quality Assessment for Studies of Diagnostic Accuracy-2 (QUADAS-2) was used to assess study quality. Meta-regression analysis was employed to investigate the underlying factors contributing to heterogeneity, alongside an evaluation of publication bias. The bivariate random-effect model was utilized to compute the primary diagnostic outcomes and their corresponding 95% confidence intervals (CIs). The pooled sensitivity, specificity, and positive and negative likelihood ratios of cfDI in cancer diagnosis were 0.70 and 0.77, 3.26 and 0.34, respectively. The overall area under the curve was 0.84, with a diagnostic odds ratio of 10.63. This meta-analysis suggested that the cfDI index has a promising potential as a non-invasive and accurate diagnostic tool for cancer. Study registration: The study was registered at PROSPERO (reference No. CRD42021276290).

Funder

Instituto de Salud Carlos III

Axencia Galega de Innovación

Publisher

MDPI AG

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