Screening Of Colorectal Cancer With Liver Metastasis -Associated MicroRNA Through Bioinformatics Methods And Discussion Of Its Clinical Significance

Objective To screen of colorectal cancer with liver metastasis-associated microRNA(miRNA)through bioinformatics methods and comp-are the expre ssion of them between primary lesion and liver metastasis,predicting the bioin dicator for the occurrence of colorectal cancer with liver metastasis.Methods In this study,we first screened miRNA expressed differentially in primary between primary lesion and liver metastasis in colorectal cancer with liver metastasis by GEO database,and screened colorectal cancer stem cellsrelated miRNA through the COREMINE Medical text mining,take their intersection as targeted miRNA.The expression levels of targeted miRNA were detected with quantitative realtime-PCR and their correlation with clinicopathologic features of colorectal cancer with liver metastasis was analyzed.At the same time,we predict the downstream targeted genes and signal pathway analysis of targeted miRNA through bioinformatics methods.Results In this study,the data were analyzed by GEO2 R online tool,and 43 differentially expressed miRNAs were obtained.On the other hand,onfirmed miRNAs that can regulate the characteristics of colorectal cancer stem cells were collected through text mining.Seven miRNAs were screened out from the two sources.The expression of these seven miRNAs was analyzed in 30 pairs of primary and liver metastases.Only hsa-miR-17 was available and used for subsequent validation.Compared with the primary lesion in colorectal cancer tissues,the liver metastasis had increased(3.48 times comparing to the primary lesion tissues)expression level of miR-17 and the difference was statistically significant(P <0.05).The expression difference of miR-17 was related to tumor primary cell differentiation and preoperative chemotherapy(P <0.05),which was not related to lymph node mrtastasis positively(P>0.05)and tumor primary location(P>0.05).Besides,we found 618 common target genes of hsa-miR-17 in three databases by searching four databases.The result that analyzed their KEGG pathway showed that the target genes were mainly involved in MAPK signaling pathways,endocytosis signaling pathways,tumor signaling pathways,axon guidance,Regulation of actin cytoskeleton,Neurotrophin signaling pathway,ErbB signaling pathway,cell cycle,insulin signaling pathways,Circadian rhythm,and a variety of tumors including colorectal cancer related pathways.Conclusions 1.Seven miRNAs related to colorectal cancer with liver metastasis were screened out,respectively: hsa-miR-20 a,hsa-miR-26 b,hsamiR-146 a,hsa-miR-17,hsa-miR-451,hsa-miR-23 a,and hsa-miR-29 a,They may be used as molecular markers to predict liver metastasis in colorectal cancer.2.The results of quantitative realtime-PCR showed that only mir-17 can reflect the expression difference of miRNA in colorectal cancer with liver metastasis.Compared with the primary lesion in colorectal cancer tissues,the liver metastasis had increased expression level of miR-17,and the expression difference of miR-17 was related to tumor primary cell differentiation and preoperative chemotherapy.3.The result that analyzed their KEGG pathway showed that miR-17 may be involved in the development of colorectal cancer with liver metastasis,it may provide the basis of the targeted therapy and improve the effect of the treatment of colorectal cancer with liver metastasis by regulating the expression of miR-17.