MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review

Abstract

Emerging evidence has demonstrated the feasibility of circulating miRNAs as robust non-invasive biomarkers for the diagnosis in colorectal cancer. The use of circulating miRNAs for the early detection of colorectal cancer (CRC) is of particular interest as it can offer a potential complementary approach to screening colonoscopy. However, the development of circulating miRNAs as "liquid biopsy" biomarkers for development into clinical screening tests has been hampered by several issues. In this article, we summarize the status of this field for the clinical utilization of miRNA biomarkers as liquid biopsies in colorectal cancer (CRC) and discuss their applications as screening tests for patients with colorectal adenoma (CRA) and CRC. Herein, we undertook a systematic search for citations in PubMed and the Cochrane Database from January 1, 2002 through December 31, 2017 as electronic sources for this study. All published studies were screened with no restriction on language, date, or country. We used database-specific combinations of the following index terms and text words, including: microRNA, colorectal cancer, serum, plasma, and exosomes. Based upon these searches, we summarize the progress and salient features of the current state of knowledge of miRNA diagnostic biomarkers in CRC, and focuses on the articles that attempt to optimize ideal methodologies to further advance their as liquid biopsies for clinical use. We conclude that the field of noncoding RNAs, particularly for the clinical use of miRNAs as liquid biopsy assays is maturing rapidly, and it is highly promising that these genomic signatures will likely be developed into clinically-viable tests for the early detection and clinical management of patients with colorectal cancer in the not so distant future.

Plasma miRNA‐based signatures in CRC screening programs

“…Sequencing miRNAs from plasma was not sufficiently established. Our experience with plasma circulating miRNAs enabled us to develop specific operating procedures for the pre‐analytical phase that ensure the reproducibility of data . The operating procedures were shared with the other hospitals participating in the external validation phase.…”

MicroRNA 32 promotes cell proliferation, migration, and suppresses apoptosis in colon cancer cells by targeting OTU domain containing 3

“…MiRNAs, one kind of small noncoding RNA molecules, possess important functions on regulating gene expression and biological processes . Previous many researchers found that the tumorigenesis was correlated with the expression change of miRNAs, suggesting that miRNAs were hopeful to be novel biomarkers used for the diagnosis and treatment of colorectal cancer . For examples, miR‐21 took part in the multiple processes of colorectal tumorigenesis, not only via regulating MAPK pathway but also via linking with Wnt/β‐catenin signaling; miR‐135 family and miR‐34 family that contacted with Wnt signaling pathway have been proved they played key roles in the development of colon cancer .…”

“…In addition, it is necessary to identify and develop more biomarkers, which contributes to the earlier detection of colorectal cancer. In most cases, colorectal cancer was developed from premalignant colorectal adenomas that gradually accumulated many mutations, further led to epigenetic alterations and finally became malignant . Previous research reported that mutations of APC and KRAS might lead to colorectal cancer .…”

“…In addition, miRNAs had a high possibility to be used as therapeutic drugs of colorectal cancer . Moreover, miRNAs could maintain a remarkably stable condition in formalin‐fixed paraffin‐embedded tissue specimens and easily extracted from them . Therefore, studying miRNAs is hopeful to identify effective biomarkers used for clinical treatments and understand more about the mechanism of cancer.…”

“…In most cases, colorectal cancer was developed from premalignant colorectal adenomas that gradually accumulated many mutations, further led to epigenetic alterations and finally became malignant. 8 Previous research reported that mutations of APC and KRAS might lead to colorectal cancer. 9,10 However, the understanding of the mechanisms caused the development and metastasis of colorectal cancer remain very little.…”