Circulating Exosomal miR-150-5p and miR-99b-5p as Diagnostic Biomarkers for Colorectal Cancer

Ya Jing Zhao; Xingguo Song; Limin Niu; Youyong Tang; Xianrang Song; Li Xie

doi:10.3389/fonc.2019.01129

Circulating Exosomal miR-150-5p and miR-99b-5p as Diagnostic Biomarkers for Colorectal Cancer

Front Oncol. 2019 Oct 23:9:1129. doi: 10.3389/fonc.2019.01129. eCollection 2019.

Authors

Ya Jing Zhao^{1

2}, Xingguo Song³, Limin Niu^{1

2}, Youyong Tang^{1

2}, Xianrang Song², Li Xie²

Affiliations

¹ School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China.
² Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
³ Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Abstract

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.

Keywords: colorectal cancer; diagnosis; exosomes; miR-150-5p; miR-99b-5p.