Background: Circulating exosomal miRNAs are potential non-invasive biomarkers for colorectal cancer. The present study aimed to validate the novel sensitive and specific exosomal miRNA biomarkers for diagnosing colorectal cancer (CRC).Patients and Methods: Exosomes isolated from the serum of CRC patients and healthy donors by ultracentrifugation were characterized using TEM, qNano, and immunoblotting. The exosomes from 2 healthy donors and 4 CRC patients were subjected to RNA isolation and miRNA sequencing. The differently expressed miRNAs from 165 primary CRC patients and 153 healthy donors were substantiated by RT-qPCR.Results: The RNA-sequence data analysis revealed that 29 exosomal miRNAs (20 downregulated and 9 upregulated) with >1.5-fold difference between CRC patients and healthy donors were selected. The serum exosomal miR-99b-5p and miR-150-5p levels were significantly downregulated in CRC patients as compared to healthy donors (p < 0.0001 and p < 0.0001, respectively) and benign disease (p = 0.009 and p < 0.0001, respectively). The expression levels of exosomal miR-99b-5p and miR-150-5p were significantly decreased in early CRC patients as compared to healthy donors (p < 0.0001 and p < 0.0001, respectively). The expression levels of exosomal miR-99b-5p and miR-150-5p were significantly increased postoperatively (p = 0.0058 and p < 0.0001, respectively).Conclusions: The present study demonstrated that serum exosomal miRNAs are promising, sensitive, specific, and non-invasive diagnostic biomarkers for CRC.Impact: This is the first study to specifically identify exosomal miR-99b-5p and miR-150-5p associated with CRC. This study, therefore, might deepen the understanding of tumor-derived exosomes for CRC diagnosis.

Cancer is a major public health problem, and >18.1 million new cancer cases are diagnosed annually. Cancer can be treated with the help of several methods, such as surgery, chemotherapy, radiotherapy, and immunotherapy. Chemoresistance causes disease relapse and metastasis, and is a main obstacle to cancer therapy. The function of exosomes has been recently highlighted in cancer treatment and therapeutic resistance. Exosomes, described as nanovesicles secreted by multiple mammalian cell types, play important roles in intercellular communication by acting as carriers of functional contents, such as proteins, non‐coding RNA (miRNA, lncRNA), mRNAs, and lipids. In addition, exosomes might participate in cancer therapeutic resistance. The present review aimed to describe the function of exosomes in different types of cancer, with emphasis on their role in chemoresistance, hoping to provide novel insights on their implications in cancer therapy.