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

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

doi:10.3389/fonc.2019.01129

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.

Highlights

Colorectal cancer (CRC) is the third most common cancer worldwide with 1.36 million new cases annually and about 700 thousand deaths [1, 2]
Exosomes are known as extracellular vesicles, with a diameter of 50–150 nm, released from different cell types [7,8,9], which are regarded as critical mediators of intercellular communications including the delivery of biological signals and selective cargo between different cells, thereby regulating multiple biological procedures [10, 11]
Exosomes from 2 healthy donors and 4 CRC patients were subjected to miRNA sequencing, and 165 CRC patients, exosomes from other 155 healthy donors, and 20 benign disease patients were subjected to qPCR verification

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide with 1.36 million new cases annually and about 700 thousand deaths [1, 2]. 50% of CRC patients are deceased as a consequence of late detection of advanced disease with localized or distant metastases [3]. These phenomena highlight and underscore a need for the identification and development of robust. MiRNAs in cancer exosomes are hormones, which are vital in mediating cancer progression and metastasis, emerging as promising biomarkers for cancer [17]. 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)

Methods

Results

Conclusion