cfDNA Integrity in Early Cancer Detection: A Review Article
Keywords:
ALU repeats, Biomarker , Cell free DNA , DNA integrity , Early cancer detection , Liquid biopsyAbstract
Background: Cell-free DNA (cfDNA) carries genetic and epigenetic information from its cells of origin. The integrity of cfDNA is the ratio of longer to shorter DNA fragments. It has emerged as a promising non-invasive biomarker for cancer diagnosis. Objective: To synthesize current evidence on the diagnostic performance of cfDNA integrity in early cancer detection. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science (2015–2026). Keywords related to cfDNA integrity, cancer, and diagnostics were used. Studies reporting quantitative integrity indices (e.g., ALU247/ALU115 ratio and LINE 1 fragments) and diagnostic accuracy metrics were included. Results: A total of 98 studies were analyzed. The cell-free DNA (cfDNA) integrity index (cfDI) was elevated in patients with lung, colorectal, breast, hepatocellular, and ovarian cancer compared with healthy subjects. Sensitivity ranges from 55% to 88%, and specificity from 70% to 95%, depending on the cancer type and cutoff. Combination with other markers (e.g., protein biomarkers, DNA methylation panels) improves performance. However, pre-analytical variability, the lack of standardized integrity metrics, and inter-study heterogeneity limit the current clinical utility. Conclusions: cfDNA integrity holds considerable potential as an adjunctive tool for early cancer detection. Standardization of pre-analytical and analytical workflows is essential, along with large-scale prospective validation, before integration into routine clinical practice.
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