Fig 1.
Representative diagrams of identification of microRNAs (miRNAs) and their targets between primary colorectal tissues and their hepatic (liver) metastases.
The Venn diagrams demonstrate the number of common differentially expressed genes (DEGs), miRNAs and the miRNA targets (red = upregulated and green = downregulated) from different Gene Expression Omnibus (GEO) datasets.
Table 1.
Common differentially expressed miRNAs between GEO dataset GSE54088 and GSE56350.
Table 2.
The common miRNAs and their common gene targets.
Table 3.
The verification of the upregulated miRNAs and their targets in miRDIP tool.
Table 4.
The verification of the downregulated miRNAs and their targets in miRDIP tool.
Fig 2.
Expression patterns in GSE29623 of common miRNAs with targets from the DEGs.
The miRNAs with a green background are commonly downregulated from Fig 1, and those with a red background are upregulated. The * represents Mann-Whitney U p-value<0.05, M0 = TNM stage I, II, III or no distant metastases and M1 = TNM stage IV or distance metastases; the number in brackets represents the case number. Note: miRNA-619 and miRNA-382 were not expressed in this dataset.
Fig 3.
The receiver operating characteristic (ROC) curve showing the area under the ROC curve (AUC), sensitivity and specificity of (A) miR-20a and (B) miRNA-495, miRNA-576-5p, miRNA-20a and miRNA-449a. The regression model was estimated based on the miRNA of interest or the combination of miRNAs of interest, and the score was calculated for colorectal cancer (CRC) metastasis. The patients were divided into M0 and M1.
Table 5.
Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) tissues.
Fig 4.
Expression patterns in the GSE39833 miRNA exosome dataset of common miRNAs with targets from the DEGs.
The miRNAs with a green background are commonly downregulated from Fig 1, and those with a red background are upregulated. The * represents a Mann-Whitney U p-value<0.05, M0 = TNM stage I, II, III or no distant metastases and M1 = TNM stage IV or distance metastases; the number in brackets represents the case number.
Fig 5.
The receiver operating characteristic (ROC) curve showing the area under the ROC curve (AUC), sensitivity and specificity of (A) miR-576-5p and miR-20a, (B) the combination of miR-576-5p and miR-20a and the combination of all six miRNAs. The regression model was estimated based on the miRNA of interest or the combination of miRNAs of interest, and the score was calculated for colorectal cancer (CRC) metastasis. The patients were divided into M0 and M1.
Table 6.
Area under curves for miRNAs in non-metastatic (M0) and distance metastases (M1) exosomes.
Fig 6.
Expression patterns of the common miRNA targets in GSE39582.
The miRNA targets with a red background are the commonly upregulated DEGs from Fig 1, and those with a green background are downregulated. The * represents a Mann-Whitney U p-value<0.05, M0 = TNM stage I, II, III or no distant metastases and M1 = TNM stage IV or distance metastases; the number in brackets represents the case number.
Fig 7.
The receiver operating characteristic (ROC) curve showing the area under the ROC curve (AUC), sensitivity and specificity of the miRNA targets (A) CDH2, KNG1 and MMP2, (B) a combination of CDH2, KNG1 and MMP2, and a combination of all nine miRNA targets. The regression model was estimated based on the gene of interest or the combination of the genes of interest, and the score was calculated for colorectal cancer (CRC) metastasis. The patients were divided into M0 and M1.
Fig 8.
Gene interaction network (A) and pathway enrichment summary of the common miRNA targets. For Figure (A), the input genes are indicated with stripes, and the green circles represent downregulated and red represents upregulated genes in CRC liver metastases, while for (B), green indicates downregulation, red indicates upregulation and gray indicates that the gene was not enriched in that pathway. The pathways are in order of their enrichment value from left to right (genes≥4, FDR<0.05, p-value<0.05). (C) Schematic summary showing possible interactions of the miRNAs and their targets in their respective pathways. Red background represents upregulation and green background indicates downregulation in CRC liver metastasis, * represents significant expression in the respective validation dataset, thick dashed black lines represent significant interactions and thin black lines represent a nonsignificant interaction. The respective pathways are represented by a gray background.
Table 7.
Enriched Reactome pathways.