Expression Of Liver-metastasis-associated MiRNA In Colorectal Cancer Patients And Its Clinical Significance

Objective:To access the expression of miRNA in plasma and cancer tissue and its clinical significance in colorectal cancer,and to evaluate its usability as non-invasive biomarker for the detection of colorectal livermetastasis.Bioinformatics is adopted to predict the target genesand signal pathway of the differentially expressed mi RNA.Methods: By analysing the chip data and using bioinformatics metho ds,to identify metastatic colorectal cancer related miRNA.The expression of candidate miRNAs in plasma of 90 colorectal cancer patients and 20 h ealthy subjects was detected by real-time quantitativePCR,formalin fixed par affin-embedded(FFPE)tumor tissues and adjacent normal tissues of twenty-five patients with non-metastatic colorectal cancer and tumor tissu es,adjacent normal tissues and liver metastases of 33 patients with colore ctal liver metastasis cancer were detected simultaneously.The diagnositic a nd prognostic value were also analyzed.GO and KEGG analysis of miR NAs were performed by bioinformatics method.Results:(1)By analysing the chip dataand using bioinformatics methods,five candidate(miR-96,mi R-99 b,miR-155,let-7a and let-7b)were identified as metastatic colorectal cancer related mi RNA.(2)Compared with non-distant metastatic colorectal cancer patients,miR-96,miR-155 and let-7a were highly expressed while the expression of miR-99 b and let-7b was down-regulated in plasma and FFPE tissues of patients with colorectal liver metastasis.(3)Compared with patients with non-diatant metastasis,plasma and tissue mi R-96,miR-155 and let-7a were upregulated while miR-99 b was down-regulated in patients with liver metastasis,and the expression of plasma let-7b was low in patients with CLM(P<0.05)(4)MiR-96 and miR-155 were down-regulated in primary intestinal tissue than that in corresponding liver metastases in patients with CLM,whereas miR-99 b was up-regulated in primary tumor.In addition,our data demonstrated that five candidate mi RNAs were associated with clinicopathologic parameters(liver metastases,clinical stage,etc.).(5)ROC curve analysis shows that the panel of plasma miR-96,mi R-99 b and let-7a have diagnostic utility,and may served as early diagnostic biomarkers of colorectal cancer patients with liver metastasis;the panel of miR-96,mi R-99 b mi R-155 and let-7a in tumor tissues have diagnostic utility.(6)survival analysis showed that mi R-96,miR-99 b both in plasma and tissue and let-7b in tissue were independent risk factors for colorectal cancer patients.Conclusion:miR-96,miR-99 b,miR-155 and let-7a/b are differentially expressed in plasma and tissues of colorectal cancer patients.Plasma mi R-96,mi R-99 b and let-7a may be served as noninvasive biomarkers for the early diagnosis of colorectal cancer patients with liver metastasis.What's more,miR-96 and mi R-99 b are of prognosis value in patients with CRLM.