Abstract

Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Highlights

  • Colorectal cancer (CRC) is one of the most common cancers worldwide

  • Our result shows down-regulation of miR16 and corresponding up-regulation of FGFR in primary tumors with metastasis (Fig. 4d), where FGFR is a receptor for FGF7 and well known to be related to proliferation and migration of endothelial cells and ­angiogenesis[25]

  • We evaluated the clinical significance of the identified miRNA-target regulations by separating primary tumor samples from the The Cancer Genome Atlas (TCGA) CRC data set, based on their resemblance to the identified regulations

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Summary

Introduction

CRC is one of the most common cancers worldwide. According to a study in ­20181, the number of CRC incidences worldwide ranked third, with mortality being second highest among all cancers. Röhr et al analyzed high-throughput sequencing data of miRNAs and mRNA transcripts from normal colon and metastasis tumor ­samples[8], and they evaluated the up/downregulations of miRNAs from individual patients to identify candidates of therapeutic targets. These studies identified miRNAs or their target regulations associated with metastasis, they have certain limitations. By investigating miRNA and mRNA profiles from primary tumor tissues with and without accompanying liver metastasis, we aim to identify miRNAs and their potential target genes that show altered expressions and may contribute to the initiation of liver metastasis.

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