Cancer protein biomarker discovery based on nucleic acid aptamers

Identification of biomarkers is essential for diagnosis, targeted therapy and prognosis evaluation of diseases, especially cancers. Currently, the number of ideal clinical biomarkers is still limited partially because of lacking efficient methods in biomarker discovery. Nucleic acid aptamers are artificial single-stranded DNA or RNA sequences that can selectively bind to various targets with high specificity and affinity. Moreover, aptamers possess desirable advantages, including easy synthesis, convenient modification, relative chemical stability and low immunogenicity. Recently, different aptamer-based strategies have been developed to facilitate the discovery of biomarkers. Based on cell-SELEX technology, the selected aptamers can be used to identify cell-surface protein biomarkers of different cancer cells. SOMAscan can analyze thousands of proteins of different biological samples, which becomes a multiplexed protein biomarker discovery platform. Additionally, secreted protein biomarkers can be discovered by aptamers screened through secretome SELEX. In order to facilitate the identification of target proteins, several covalent cross-linking strategies have been developed, such as aptamer-based affinity labeling (ABAL), DNA-templated aptamer and protein-aptamer template (PAT). In this review, we mainly highlight the emerging nucleic acid aptamer-based biomarker discovery strategies and demonstrate their unique technological advantages in discovering cancer biomarkers. The challenges and perspectives of aptamer-based methods are also discussed.