Identification Of MicroRNA-181 As A Promising Biomarker For Predicting The Poor Survival In Colorectal Cancer

Background:Increasing evidence has indicated that dysregulation of microRNA-181(miR-181)plays a vital role in the initiation and development of colorectal cancer(CRC),and might be associated with the prognosis of CRC.However,inconsistent findings have hindered its clinical application.Therefore,we carried out a meta-analysis to evaluate the prognostic significance of miR-181 expression in colorectal cancer and to further explore its biological function.Methods:Electronic databases were searched to confirm eligible studies which evaluated the prognostic value of miR-181 expression for CRC patients from inception through October 2018.Patients' clinicopathological characteristics and survival results were collected from included studies.Pooled hazard ratio(HR)and its 95%confidence interval(Cl)were assessed with a random-effects model or fi xed-effects model.At the same time,we performed a synthesized bioinformatics analysis to probe the function of miR-181 in CRC.Results:A total of 1017 patients were included in 9 studies.NOS scores in all literatures were above 6.The results revealed that elevated expression levels of miR-181 indicated significantly worse overall survival rates(HR?1.75,95%Cl:1.26-2.43,P<0.05).Subgroup analysis showed that miR-181 may be a more effective biomarker for predicting poor survival in Asian patients with CRC.Different categories of miR-181 including miR-181a and miR-181b could predict worse overall survival rates of CRC patients.Meanwhile,the target genes of miR-181 were identified and enriched into several important gene ontology categories and signaling pathways including miRNAs in cancer,pathways in cancer,proteoglycans in cancer,colorectal cancer,FoxO signaling,PI3K-Akt signaling,VEGF signaling,HIF-1 signaling,mTOR signaling and cAMP signaling pathway,which were confirmed highly involved in the initiation and progression of CRC.In addition,the protein-protein interaction networks were constructed by miR-181 targets for screening the hub nodes and significant modules,which were also considerablely associated with the molecular pathogenesis of CRC.Conclusions:The present study demonstrated that miR-181 could be a promising biomarker with predictive value for prognosis for CRC patients.The key signal pathways and target genes of miR-181 should be further discussed.