A circulating exosomal microRNA signature for the detection of minimal residual disease after curative resection in patients with stage II and III colorectal cancer.

209 Background: For patients with pathological Stage (pStage) III and high-risk pStage II colorectal cancer (CRC), postoperative adjuvant chemotherapy (ACT) following curative resection of tumors is recommended to prevent recurrence caused by minimal residual disease (MRD). However, considering its survival benefits, toxicity, and medical costs, optimal indication, regimen and duration of ACT remain unclear. For the clinical decision-making for the selection of patients who will benefit from postoperative ACT, the identification of predictive 102molecular biomarkers capable of monitoring MRD after curative resection of tumors is the primary challenge, thereby contributing to improved prognosis of patients with CRC. In this study, we established an exosomal microRNA (exo-miRNA)-based liquid biopsy assay to predict recurrence and detect MRD in patients with pStage II and IIII CRC. Methods: A comprehensive biomarker discovery was performed through analyzing multiple tissue-based and exosome-based genome-wide miRNA profiling. The tissue-based dataset included 258 patients 17with CRC, while the exosome-based dataset comprised a total of 308 patients. For clinical exo-miRNA-based biomarker validation, we enrolled 325 patients with pStage II and III CRC. Exosomes were extracted from plasma specimens obtained one month after curative surgery, and biomarker validation was performed by quantifying exo-miRNAs using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Results: 26 miRNAs were differentially expressed between patients with recurrence and without recurrence in the tissue-based miRNA profiling (|Log 2 fold-change| >0.5 and P