Aptamer-based discovery of MARK2 as a potential biomarker for targeted imaging and exosome detection of metastatic colorectal cancer.

Abstract

Metastatic colorectal cancer (CRC) has a high recurrence rate, rapid progression and poor prognosis. Therefore, the discovery of metastatic related biomarkers is crucial for early diagnosis and treatment. Aptamer W14 was previously developed through cell-systematic evolution of ligands by exponential enrichment (SELEX), which could specifically bind to metastatic CRC cells. In this study, using an aptamer-based target discovery strategy, microtubule-affinity regulating kinase 2 (MARK2) was identified as the target protein of W14 and confirmed to be involved in the migration and invasion of CRC. The combination of aptamer W14 and quantum dots (QD) for specific recognition of clinical tissue samples revealed the potential of W14-QD probe based on MARK2 as a targeted imaging tool for metastatic CRC tissue. In addition, further experiments have confirmed for the first time the role of exosomal MARK2 in CRC metastasis. Thus, we developed a W14-based molecular aptamer beacon (MAB-W14) for one-step to quantify MARK2-positive exosomes in the plasma of CRC patients, and demonstrated that MAB-W14 was a promising liquid biopsy tool for predicting CRC metastasis. This study provides a systematic and novel approach for investigating potential biomarkers, and offers promising molecular probes for the diagnosis and treatment of metastatic CRC.