Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum

• Published in: Nature communications 2021-06, Vol.12 (1), p.3515-12, Article 3515
• Main Authors: Cai, Shenglin, Pataillot-Meakin, Thomas, Shibakawa, Akifumi, Ren, Ren, Bevan, Charlotte L., Ladame, Sylvain, Ivanov, Aleksandar P., Edel, Joshua B.
• Format: Article
• Language: English
• Subjects: 140/125; 631/337/384/331; 631/57/2265; 631/67/1857; 639/925/350; 9/10; Biomarkers; Biomarkers, Tumor - analysis; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Blood; Blood circulation; Body fluids; Circulating MicroRNA - analysis; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Diagnosis; Diagnostic systems; Early Detection of Cancer - instrumentation; Early Detection of Cancer - methods; Fluorescence; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Humanities and Social Sciences; Humans; Liquid Biopsy; Male; Medical diagnosis; MicroRNAs; MicroRNAs - analysis; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Monitoring; multidisciplinary; Multiplexing; Nanopores; Post-transcription; Prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Real-Time Polymerase Chain Reaction; Remission; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Selectivity; Sensitivity and Specificity; Single Molecule Imaging - methods; Telemedicine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23497-y

MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer. miRNA profiling from patient blood can be used for cancer diagnosis. Here the authors present an electro-optical nanopore sensing platform which allows sensitive and specific miRNA detection directly in human serum and apply to monitoring of miR-141-3p and miR-375-3p in different stage of prostate cancer.