Exosome-Protein-microRNA-OneStop (Exo-PROS) biosensor: a new liquid biopsy for cancer screening and early detection

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Molecular & Cellular Analysis Technologies
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PROJECT SUMMARY Current cancer screening tests, such as low dose computed tomography (LDCT) for lung cancer andcolonoscopy for colorectal cancer, are challenged by low sensitivity, high false positive rate, limited tumorinformation, uncomfortable or invasive procedures and high cost. Liquid biopsy that detects circulatingbiomarkers, allows sequential monitoring of cancer development, complements medical imaging and risk factordata to provide a more comprehensive portrait of cancer, and thus it has shown great promise as the in vitrodiagnostics for cancer. Exosomal proteins and exosomal microRNAs are promising cancer biomarkers forliquid biopsy, and have shown very high sensitivity and specificity in diagnosing many cancers. Unfortunatelycurrent detection technologies, such as ELISA, LC-MS, qRT-PCR, microarray and next generation sequencing,are tedious, expensive and time consuming, which limits their clinical utilities as screening tests. Moreover,many methods cannot distinguish tumor-derived exosomes from their non-tumor counterparts, and thus sufferfrom poor detection sensitivity and specificity. To address these challenges, we have developed a surfaceplasmon resonance (SPR)-based, molecular beacon-assisted liquid biopsy device, named Exosome ProteinmicroRNA OneStop (Exo-PROS) biosensor. This biosensor can capture tumor-derived exosomes usingcancer-overexpressed proteins. It can also provide one-stop quantification of surface proteins and intra-vesicular microRNAs of captured exosomes on a single device within 4 hours. The effective separation oftumor-derived-exosomes from interfering exosomes (such as normal-cell-derived exosomes) and thecombination of exosomal protein and microRNA biomarkers may significantly increase the diagnostic accuracy.We have successfully used the Exo-PROS biosensor to measure exosomal EGFR and EGFR+ exosomal miR-21 in cell culture medium and lung cancer patient serum samples. The biosensor showed higher sensitivity andspecificity than ELISA and qRT-PCR in distinguishing cancer from normal controls. In this study, we proposeto (1) advance the development of the Exo-PROS biosensor to improve its sensing performance and to realizemultiplexed biomarker detection; (2) demonstrate its clinical utility in lung cancer screening and early detection,and explore the diagnostic value of exosomal protein and microRNA combined biomarkers in cancer, whichhas not yet been investigated. We will evaluate the detection sensitivity and specificity of Exo-PROS biosensorin distinguishing nonsmall cell lung cancer patients from healthy controls and smokers with benign solitarypulmonary nodule at high risk for lung cancer. We will demonstrate the superior sensing performance of Exo-PROS biosensor over ELISA and qRT-PCR assays. We expect to develop the Exo-PROS biosensor into ahighly accurate, simple, fast, and cost-effective liquid biopsy test for cancer screening and early detection.