Abstract 727: Detection of early-stage lung cancer using a liquid biopsy test based on extracellular vesicle proteins

Abstract

Abstract We have recently conducted a study to evaluate the use of proteins associated with extracellular vesicles (EVs) isolated using an alternating current electrokinetic (ACE) system for the detection of early stage (I & II) non-small cell lung cancer (NSCLC). Most lung cancers are diagnosed at advanced stages when treatments are less effective, pointing to the need for developing non-invasive screening strategies such as liquid biopsies. We tested the feasibility of detecting the presence of early stage (I-II) lung cancer using protein biomarkers carried by EVs in patient blood. Using an ACE microelectrode array, EVs were purified from NSCLC patient (N = 62; Stage I = 39, Stage II = 23) or control plasma (N = 390) and tested for the presence of cancer biomarker proteins with bead-based multiplex immunoassay kits. A machine learning algorithm based on recursive feature elimination with cross-validation was developed to identify the most important features for differentiation between cases and controls. The algorithm identified 10 protein biomarkers that were able to distinguish between the NSCLC and control patient samples with a receiver-operator characteristic (AUC) of 0.986 (95% CI: 0.976 - 0.996). Sensitivity was 66.1% at 99.2% specificity, rising to 79.0% and 93.6% sensitivity at 98.2% and 95.1% specificity, respectively. When further stratified, Stage I sensitivity was 53.8% and stage II sensitivity was 86.7% at the 99.2% specificity level. These results suggest that it is possible to detect early-stage NSCLC when treatments may be more effective, that EVs may carry the earliest signals of cancer development, and that a test based on blood-based EV-protein biomarkers can yield high sensitivity and specificity. Our results warrant investigation in larger datasets to validate the current observations with the potential application of this methodology for routine screening of at-risk populations. Citation Format: Juan P. Hinestrosa, Jean M. Lewis, Gregor Schroder, Heath I. Balcer, Razelle Kurzrock, Rajaram Krishnan. Detection of early-stage lung cancer using a liquid biopsy test based on extracellular vesicle proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 727.