Transcriptome analysis and machine learningdevelops a lncRNA‐miRNA‐mRNA signature for prognosis,diagnosis, and therapy of colorectal cancer

Background: The clinical significance of potential molecularbiomarkers and therapeutic targets related to the progression ofcolorectal cancer (CRC) from early stages to advanced metastasisremain largely unexplored. Moreover, the regulation andcrosstalk among different cancer-driving molecules includingmessenger RNAs (mRNAs), long non-coding RNAs (lncRNAs)and micro-RNAs (miRNAs) in the transition from stage I to stageIV remained to be clarified, which is the aim of this study.Materials and Methods: In order to explore conserved andstage-specific biomarkers two separate datasets were analyzed.Then, by the means of Robust Rank Aggregation (RRA) andweighted gene co-expression network analysis (WGCNA) weidentified distinct lists of differently expressed genes (DEGs)for each group. Afterwards, integrated systems biology analysesincluding mRNA-miRNA-lncRNA regulatory network, enrichmentanalysis, expression analyses, survival analysis andsix machine learning-based algorithms were also employed toidentify a lncRNA‐miRNA‐mRNA signature for prognosis, diagnosisand treatment of CRC. Ultimately, for further validationusing RT-qPCR, we have used CRC clinical normal/tumorsamples.Results: By combining distinct results from RRA and WGCNAwe have identified a list of the most significant stage-specificDEGs. Then, a total number of ۳۷ DEGs were selected asconserved across all stages of CRC (conserved DEGs). Wealso found DE-miRNAs and DE-lncRNAs highly associatedto these conserved DEGs. Finally, based on the integrated approachespotential therapeutic targets, predictive and prognosticbiomarkers in CRC were identified.Conclusion: Findings of the present study provide new insightinto CRC pathogenesis across all stages, and suggests futureassessment of the functional role of these biomarkers in the developmentof CRC.

کلیدواژه ها:

Colorectal_cancer ، machine_learning ، deep_learning ، systems_biology ، lncRNA