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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Protein Panel of Serum-Derived Small Extracellular Vesicles for the Screening and Diagnosis of Epithelial Ovarian Cancer

“…A recent study trying to diagnose multiple types of early-stage cancer isolated and purified EVs in plasma to determine the levels of potential protein markers by immunoassay. By utilizing artificial intelligence, 13 EV protein markers were analyzed to predict the likelihood of malignancy [ 31 ]. CA19-9 is commonly used to monitor the therapeutic efficacy and recurrence of pancreatic cancer.…”

“…CA19-9 is commonly used to monitor the therapeutic efficacy and recurrence of pancreatic cancer. The novel diagnostic method contains CA19-9 and has excellent diagnostic performance for early-stage pancreatic cancer (95.7% detection rate), while detection of early-stage ovarian cancer and bladder cancer were 74.4% and 43.8% [ 31 ], suggesting the importance of characteristic biomarkers for diagnosing specific cancer type. The novel diagnostic protein panel in our study included CA125, a specific marker for ovarian cancer, and its performance in diagnosing ovarian cancer including their early-stage disease and discriminating between benign and malignant ovarian tumors in the population was more effective than CA125.…”

Liquid biopsy: current technology and clinical applications

“…Hinestrosa et al [ 86 ] utilized biomarkers present in circulating extracellular vesicles in an attempt to detect early-stage, curable pancreatic, ovarian, and bladder cancers. Pathologically confirmed stage I and II cancer cases were compared to control subjects in a pilot study.…”

Liquid biopsies to occult brain metastasis

“…EVs with artificial intelligence hinted at detecting early-stage 1 and 2 pancreatic cancers. Liquid biopsies based on EVs are getting popular and could be a revolution in liquid biopsy-based cancer diagnostics [ 239 ].…”