Label-Free Electrochemical Biosensors for Early Detection of Breast Cancer: A Systematic Review and Meta-Analysis of miRNA (miR-21, miR-155) and Exosome-Based Platforms
Breast cancer is the most prevalent cancer among women in the world and early diagnosis of cancer is the most important predictor of long-term survival. While currently popular screening tests such as mammograms and confirmatory tissue biopsies have drawbacks such as invasiveness, expense and less sensitivity in dense breast tissue, there has been a growing interest in minimally invasive molecular liquid-biopsy biomarkers. Among the analytes, miRNAs (in particular miR-21 and miR-155) and tumour derived exosomes are promising analytes because of their tight mechanistic relation to the oncosignalling pathways and/or their stability in biofluids. Alternatively, using a label free electrochemical biosensor in which the change of electron transfer at the interfaces is detected by the addition of the target molecule, can also be rapid, cost efficient and very sensitive for a fluorescence or enzyme linked assay. Systematic review and meta-analysis of the label-free electrochemical biosensing platforms used to detect miR-21, miR-155 and exosomes in the context of breast cancer diagnosis and prognosis are presented for the period 2021-2026. According to PRISMA guidelines, twenty primary studies were found from PubMed, ScienceDirect, Scopus, and Web of Science and were assessed for their sensor architecture and nanomaterial transducer, recognition element, limit of detection, linear dynamic range and clinical validation. The pooled estimates from the eleven diagnostic accuracy studies are 90% (0.88–93%) for the sensitivity and 92% (87–95%) for the specificity, and the summary area-under-curve is 0.94 (0.86–0.98). These application areas, such as electrode nanoarchitecture, aptamer/PNA probe design and CRISPR-assisted signal amplification, become the key areas of diagnostic performance, whereas reproducibility, interference with the biological matrix, and limited clinical-cohort validation appear to be the major barriers to bring laboratory prototypes to the point-of-car.