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  • Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test.

Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test.

Communications medicine (2022-05-24)
Juan Pablo Hinestrosa, Razelle Kurzrock, Jean M Lewis, Nicholas J Schork, Gregor Schroeder, Ashish M Kamat, Andrew M Lowy, Ramez N Eskander, Orlando Perrera, David Searson, Kiarash Rastegar, Jake R Hughes, Victor Ortiz, Iryna Clark, Heath I Balcer, Larry Arakelyan, Robert Turner, Paul R Billings, Mark J Adler, Scott M Lippman, Rajaram Krishnan
ABSTRACT

Detecting cancer at early stages significantly increases patient survival rates. Because lethal solid tumors often produce few symptoms before progressing to advanced, metastatic disease, diagnosis frequently occurs when surgical resection is no longer curative. One promising approach to detect early-stage, curable cancers uses biomarkers present in circulating extracellular vesicles (EVs). To explore the feasibility of this approach, we developed an EV-based blood biomarker classifier from EV protein profiles to detect stages I and II pancreatic, ovarian, and bladder cancer. Utilizing an alternating current electrokinetics (ACE) platform to purify EVs from plasma, we use multi-marker EV-protein measurements to develop a machine learning algorithm that can discriminate cancer cases from controls. The ACE isolation method requires small sample volumes, and the streamlined process permits integration into high-throughput workflows. In this case-control pilot study, comparison of 139 pathologically confirmed stage I and II cancer cases representing pancreatic, ovarian, or bladder patients against 184 control subjects yields an area under the curve (AUC) of 0.95 (95% CI: 0.92 to 0.97), with sensitivity of 71.2% (95% CI: 63.2 to 78.1) at 99.5% (97.0 to 99.9) specificity. Sensitivity is similar at both early stages [stage I: 70.5% (60.2 to 79.0) and stage II: 72.5% (59.1 to 82.9)]. Detection of stage I cancer reaches 95.5% in pancreatic, 74.4% in ovarian (73.1% in Stage IA) and 43.8% in bladder cancer. This work demonstrates that an EV-based, multi-cancer test has potential clinical value for early cancer detection and warrants future expanded studies involving prospective cohorts with multi-year follow-up.