Electrochemical biosensing of circulating MicroRNAs in endometrial Cancer

The global incidence of endometrial cancer (EC) is increasing; however, current diagnostic and surveillance methodologies, which rely on invasive sampling and imaging, are insufficient for detecting early molecular alterations and accurately predicting treatment resistance and recurrence. Circulating microRNAs (c-miRNAs) are promising minimally invasive biomarkers that reflect tumor biology and disease dynamics. Nevertheless, their application in laboratory medicine is limited due to their low concentrations in circulation, the high degree of sequence homology among miRNA family members, interference from isomiRs, and preanalytical variability, all of which compromise reproducibility and inter-laboratory comparability. Electrochemical biosensing is an emerging analysis platform in clinical chemistry because of its ability to directly transduce signal changes as a result of hybridization, high turnaround, capability to operate using low sample volumes, and compatibility with automated and decentralized workflows. The nanostructuring of electrodes, engineering of probes, and integration of microfluidic systems have significantly enhanced the sensitivity of analytical processes and improved multiplexing capabilities. However, some of the critical barriers to translation, such as the absence of standardized calibration and normalization protocols, inadequate validation in clinically relevant matrices (plasma/serum) and a complete comparison of methods with established reference procedures, such as quantitative PCR and digital PCR, are still present. This review critically evaluates c-miRNA signatures and electrochemical biosensing platforms in laboratory medicine, examining validation, quality assurance, and regulatory processes for clinically actionable assays supporting early detection, risk stratification, therapy monitoring, and recurrence assessment. The future use of clinical methods will hinge on their reproducibility in actual matrices, their traceability to reference methods, and their accreditation.