LncRNAs Associated With Postoperative Recurrence Of Early Colorectal Cancer Were Screeneed:A Study Based On TCGA And GEO Databases

Background:Colorectal cancer is a common malignant tumor of the digestive tract.Increase mortality with the living environment and life-style change^[1].In recent years,research on the pathogenesis,diagnosis,treatment and monitoring of colorectal cancer have made great progress.Various new surgical methods,new types of chemotherapy drugs,and gene molecular tests have been applied in clinical practice and achieved good clinical effect,but the mortality rate of colorectal cancer is still growing（National data is absent.In Xia Men,China,epidemiological analysis of colorectal cancer shows:from 2005 to 2014,the mortality rate of colorectal cancer in Xia Men residents was 10.69/100,000,an average annual increase of 9.35%,men death rate is 1.40 times of women,s）^[2].Epidemiological studies have shown that the incidence of colon cancer is increasing,and the incidence of rectal cancer is decreasing^[3].Postoperative recurrence and metastasis of colorectal cancer are the main reasons for the poor long-term outcome of patients with colorectal cancer.TNM staging of colorectal cancer is the main risk factor for postoperative recurrence of colorectal cancer.The later thepostoperative stage of colorectal cancer,the higher the risk of recurrence,the 5-years survival rate of early colorectal cancer patients is 90.1%,and the advanced patients^’is only 10.4%.Although the long-term efficacy of early colorectal cancer patients is significantly better than that of advanced colorectal cancer patients;however,nearly 10%of patients with early colorectal cancer had poor long-term efficacy due to postoperative recurrence^[4].Screening for biomarkers for postoperative recurrence of colorectal cancer with high specificity and high sensitivity,early intervention in patients with high recurrence risk factors may improve their long-term efficacy.In recent years,a large number of studies have found that lncRNA plays an important role in the occurrence,progression,metastasis and recurrence of various tumors,providing a new direction for studying tumor pathogenesis,treatment and diagnosis.Studies have reveal that lncRNA and DNA,RNA,and protein interaction regulation networks are key factors in the pathogenesis and progression of colorectal cancer.They play a dual role of oncogenes and tumor suppressor genes,and can be used as biomarkers for diagnosis,treatment,and prognosis of colorectal cancer patients.[5].The literature review found that the current study of lncRNA and colorectal cancer,Progression,early recurrence of colorectal cancer was reported,but there are few reports on the characteristics of lncRNA recurrence in early colorectal cancer.In this paper,we explored the expression of colorectal cancer gene expression in the database,using the early colorectal cancer lncRNA and mRNA expression profiles and clinical information bioinformatics research,found that postoperative recurrence of early colorectal cancer features lncRNA,construct multi-lncRNA model to predict the postoperative recurrent of early colorectal cancer.Objective:Identify the differential lncRNA and genes in early postoperative recurrence of colorectal cancer,construct a multi-lncRNA model to assess the risk of postoperative recurrence of colorectal cancer.Methods:Using lncRNA and mRNA expression data and clinical information data of colorectal cancer tissues and adjacent normal tissues samples in TCGA and GEO databases,we can identify the differential expression of lncRNA and mRNA in colorectal cancer relative to normal colorectal tissues.Then,the single-factor COX proportional hazards regression model was used to screen the lncRNA associated with disease-free survival（DFS）of early colorectal cancer,and the multi-lncRNA model of early colorectal cancer recurrence was constructed with the weighted values of regression coefficient and expression level.The COX proportional hazard regression model evaluated the predictive prognostic independence of the model.Using this model,early colorectal cancer tissue samples were divided into two groups:high recurrence risk and relatively low recurrence risk.The differential expression of lncRNA and mRNA was identified in the two groups and the colorectal cancer was screened for the same differential expression compared with normal colorectal tissue.The easier it is to relapse lncRNA and mRNA.Subsequently,in the range of these differential lncRNAs and mRNAs,the target genes of lncRNA were identified by Pearson correlation analysis and the biological functions of these lncRNA target genes were explained by KEGG pathway analysis.Finally,the reliability of the model is verified in an independent data set.Results:Within the identification of 110 differentially expressed lncRNA and 5484 differentially expressed mRNAs in colorectal cancer relative to normal colorectal tissues,a single COX proportional hazard regression model was used to screen lncRNAs associated with early colorectal cancer DFS in the training set（GSE14333）.Related early colorectal cancer DFS 10 lncRNAs were used to construct a classification model for postoperative recurrence of early colorectal cancer.According to the median value of the classification model,135 patients were divided into high-risk group for postoperative early colorectal cancer recurrence（high-risk group）and low-risk group for postoperative early colorectal cancer（low-risk group）.DFS has a significant difference（HR=8.2326,p value=0.0009）.Multivariate COX proportional hazard regression model results show that the prognostic predictive performance of this marker is independent of other clinical features.Subsequently,the differential expression of lncRNAs and mRNAs between the high-risk group and the low-risk group were identified,and 12 and 672 lncRNA and mRNA with the same differentially expressed colorectal cancer compared to the normal colorectal cancer and the higher the difference,the more likely the recurrence.In the range of these differential lncRNA and mRNA,use Pearson correlation analysis to identify the target gene of lncRNA,and use the KEGG pathway analysis of the target gene to explain the biological functions of these lncRNA,mainly involving multiple metabolic pathways,immune system related pathways,signals Conduction path.Finally,the reliability of the multi-lncRNA classifier was verified using the independent data set GSE17536.79 early colorectal cancer patients were divided into high-risk group and low-division group by the median score.There was a significant difference in disease-free survival between the two groups（HR=6.2245,p value=0.0071）.The characteristics of high recurrence risk lncRNA are also reproducible.Conclusion:The 10 lncRNAs associated with DFS in early colorectal cancer have independent predictive potential for early colorectal cancer recurrence risk.Abnormal expression of 12 features of high recurrence risk lncRNA may cause changes in target gene expression,leading to disorder of related metabolic pathways,immune system pathways,signal transduction pathways or aggravation of disorders,making patients with early colorectal cancer more likely to relapse,early lncRNA associated with a high risk of colorectal cancer may be a target for improving the prognosis of these patients.