Abstract 2610: A high performance blood test for multiple cancer early screening

Introduction: Early detection is critical to improving cancer patient survival and quality of life. Cell-free DNA (cfDNA) methylation profiling is a promising diagnostic approach for early detection of cancer, even before symptoms appear. We previously reported a non-invasive and cost-effective methylation test, Aurora, which is able to detect three major cancer types with high specificity and sensitivity especially at early stages (I/II), including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC). We have improved this test to include two additional major cancer types, gastric cancer (GC) and esophageal cancer (EC). Taking together, these five cancer types represent 56% of new cancer cases and 60% of cancer-related deaths in China. Methods: We developed a novel high-throughput targeted methylation profiling platform, Aurora 2.0 (an improved version of Aurora 1.0, as presented in AACR 2020), to efficiently enrich and capture cancer-specific DNA methylation markers in plasma, prior to analysis via next-generation sequencing on a MiSeqDx system. About 100 cases each for GC and EC patients (mostly at Stage I/II), together with ~200 healthy controls, have been analyzed by using Aurora 2.0 and used for model development and validation. Results and Discussion: cfDNA methylation profiles have been obtained from 409 plasma samples, comprising 206 healthy controls, 98 GC and 105 EC patients. Logistic regression model has been developed with the Area Under Curve (AUC) of 94.0% and 93.5% for GC and EC, respectively. Overall, the performance (AUC) of Aurora 2.0 for LC/BC/CRC/GC/EC are 97.3%, 96.2%, 92%, 94% and 93.5%, respectively. An independent cohort (~2,000 plasma samples, five cancer types including lung, breast, colorectal, gastric and esophageal cancers with healthy controls) study is undergoing to further validate this test prospectively. The superior performance and cost-effectiveness (~$100) of the test could make early cancer screening of multiple major cancers in symptom-free and average-risk populations more achievable. Citation Format: Linhao Xu, Jun Wang, Weifeng Ma, Xin Liu, Ting Yang, Sihui Li, Qian Hu, Jinsheng Tao, Zhujia Ye, Zhiwei Chen, Jian-Bing Fan. A high performance blood test for multiple cancer early screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2610.