Introduction: Colorectal Cancer (CRC) is the third most common cancer in the world, with 1 in 13 people affected worldwide. The miRNA profile of CRC has been shown to be dysregulated throughout the different CRC stages. However, current miRNAs are non-specific to CRC and cannot be used as a tool for tracking CRC progression. Therefore, this study aims to use a Next Generation Sequencing (NGS) approach to discover novel miRNAs to track the progression of CRC.
Methods: A total of 28 patients were recruited for this study and 3 samples were taken from each patient (plasma exosomes, CRC tissue and adjacent normal tissue). The miRNA within exosomes were sequenced using the Illumina NextSeq 500. The lme4 package was employed to perform linear mixed modelling on the normalised miRNA counts across CRC stages for tissue and exosomes. Statistically significant differences in miRNA expression across CRC cancer stages, and between normal and CRC tissues was determined using likelihood ratio tests.
Results: A total of 425 and 42 miRNAs were found to be differentially expressed when comparing CRC tissues to adjacent normal tissues, and for exosomes across CRC progression, respectively. A total of 11 differentially expressed miRNAs were shared between tissues and exosomes including miR-7975, a novel miRNA in the field of CRC progression. Our bioinformatic analysis indicates that miR-7975 potentially targets gene ACVR1.
Conclusions: We have identified 11 miRNAs (including novel miRNA miR-7975) that could potentially be used as circulating biomarkers for CRC progression, and should be investigated in further validation studies.