Int J Biol Sci 2021; 17(2):562-573. doi:10.7150/ijbs.48782


Exosomal circRNAs as novel cancer biomarkers: Challenges and opportunities

Shuai Wang1#, Yanhan Dong2#, Anjing Gong3, Huimin Kong4, Jinning Gao2, Xiaodan Hao2, Yongmei Liu1, Zibo Wang1, Yuqiao Fan1, Chengyu Liu1✉, Wenhua Xu1✉

1. Department of Inspection, The medical faculty of Qingdao University, Qingdao 266003, China.
2. Institute of Translational Medicine, Qingdao University, Qingdao, 266003, China.
3. Department of Neurosurgery, The affiliated hospital of Qingdao University, Qingdao 266003, China.
4. School Hospital, Shandong University of Science and Technology, Qingdao 266003, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Wang S, Dong Y, Gong A, Kong H, Gao J, Hao X, Liu Y, Wang Z, Fan Y, Liu C, Xu W. Exosomal circRNAs as novel cancer biomarkers: Challenges and opportunities. Int J Biol Sci 2021; 17(2):562-573. doi:10.7150/ijbs.48782. Available from

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Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.

Keywords: CircRNAs, exosomes, exosomal circRNAs, liquid biopsy, biomarkers