Identification Of Diagnostic LncRNAs And Prognostic LncRNAs In Colorectal Cancer By Bioinformatics Analysis

Objective:Colorectal cancer is one of the main causes of tumor death worldwide.Although the methods of diagnosis and treatment have been greatly improved in recent years,there is still no effective diagnostic markers,and the patient's prognosis has no obvious improvement.LncRNA is a kind of long-chain non-coding RNA,which can regulate gene expression,and its expression dysregulation is involved in the occerrence and development of colorectal cancer.A growing number of studies have shown that IncRNA has potential as a diagnostic marker and its diagnostic model can predict a patient's prognosis.Our study aimed to find IncRNAs related to the diagnosis and prognosis of colorectal cancer,and lay a foundation for the early diagnosis,prognosis and individualized treatment of colorectal cancer patients.Methods:6 colorectal cancer datasets were collected in the GEO database,3 of which were used as screening and the others were used as validation,and analyzed the datasets using the online analysis tool GE02R to obtain the corresponding differentially expressed IncRNrAs.Moreover,3 validation datasets were uesd to verify the expression level of candidate IncRNAs.The GEPIA database was used to verify the expression and methylation level of candidate IncRNAs in various tumor tissues.The data of mRNA-seq and corresponding clinical follow-up information from rectal adenocarcinoma samples retrieved and downloaded from the TCGA database,including 167 rectal adenocarcinoma tissues and 10 normal rectal epithelial tissues,trained as subjects set.In addition,TCGA colon adenocarcinoma mRNA-seq data and corresponding clinical follow-up data were collected and downloaded,including 480 colon adenocarcinoma tissues and 41 normal colon epithelial tissues,trained as validation set.We performed differential IncRNAs analysis in rectal adenocarcinoma tissues and normal rectal epithelial tissues.Univariate COX regression analysis of IncRNAs differentially expressed in rectal adenocarcinoma was performed to obtain prognostic-related IncRNAs,and further screened using LASSO regression models and multivariate COX regression analysis to obtain the most prognostic-related IncRNAs and construct a linear risk model based on IncRNAs expression profiles to predict patient's prognosis.The effectiveness of the risk model in predicting the prognosis of patients was validated with partial rectal adenocarcinoma samples,partial colon adenocarcinoma samples and all colon adenocarcinoma samples.Results:There were 6 significant differentially expressed IncRNAs in the three GEO colorectal cancer datasets(fold change?2,P<0.05),of which 2 were up-regulated IncRNAs(ENSG00000256249,LINC00858)and 4 were down-regulated IncRNAs(CDKN2B-AS1,DPP10-AS1,FLJ22763,ENSG00000225335).Other 3 GEO colorectal cancer datasets verified that 6 IncRNAs were stably differentially expressed,and GEPIA database validation result suggested that DPP10-AS1 and FLJ22763 were differentially expressed,and DPP10-AS1 was differentially expressed in colorectal cancer only,while FLJ22763 was differentially expressed in both liver cancer and colorectal cancer.The LncBook database suggested that DPP10-AS1 was hypermethylated in normal colonic epithelium and partially methylated or unmethylated in tumor tissue.Compared with normal tissues adjacent,14 prognostic-related IncRNAs were screened in rectal adenocarcinoma,7 of which highly expressed(AC079789.1?AL121987.1?AC011498.4?AC083906.3?AC100803.3?AC106900.2?ST8SIA6-AS1),were associated with lower survival rates,and other 7 lncRNAs(LINC02188?GATA2-ASI1?AL136418.1?AC097358.2?CYP4A22-AS1?TLX1NB?AL162254.1)highly expressed were associated with higher survival rates.Moreover,a risk model was constructed based on the 14-lncRNAs signature.In the internal validation set of rectal adenocarcinoma and external validation of colon adenocarcinoma,the survival time of high-risk patients was significantly shorter than low-risk patients(P<0.05).Conclusion:LncRNA DPP10-AS1 was specifically and differentially low expressed in colorectal cancer tissues,and was partially methylated or unmethylated in tumor tissues.The high expression levels of LINC02188,GATA2-AS1,AL136418.1,AC097358.2,CYP4A22-AS1,TLX1NB,AL162254.1 were positively correlated with the prognosis of patients in colorectal cancer,and the high expression levels of AC079789.1,AL121987.1,AC011498.4,AC083906.3,AC100803.3,AC106900.2,ST8S IA6-AS1 were negatively correlated with the prognosis of patients in colorectal cancer.The 14-IncRNAs signatire risk model can effectively classify patients with colorectal cancer into a high-risk group with poor prognosis and a low-risk group with good prognosis.