Profiling the expression of LncRNAs involved in colorectal cancer progression in search for suitable diagnostic biomarkers

Backgrounds: Colorectal cancer (CRC) is among the most lethal cancers in both women andmen, worldwide. This high mortality rate can be prevented by early diagnosis and thus moreefficient treatment strategies. To that end, introducing more effective and clinically relevantbiomarkers would be very important. Recent comprehensive transcriptome studies highlightedthe importance of differentially expressed LncRNAs (DELs) in the tumorigenesis pathways ofCRC. In this study, we aimed to construct networks of co-expressed genes (modules) involved inCRC in search for novel LncRNAs that can serve as diagnostic biomarkers.Materials and Methods: This project has been carried out using public RNA-seq data sets ofNCBI (bio project: PRJEB۲۷۵۳۶). Data from ۶۲ samples (tumor and adjacent normal tissue) infastq file format were retrieved from SRA. Differential expression analysis was performed byDESeq۲ package in R and by utilizing WGCNA algorithm. Genes that exhibit a similarexpression pattern were classified into a number of modules.Results: We found ۲۵۱ upregulated and ۱۹۲ downregulated LncRNAs in our analysis of CRCsamples. WGCNA clustered all the genes into ۲۰ distinct modules. Our gene of interest,APOBEC۳A (LFC = -۳.۲) was highly co-expressed with these novel DELs: RP۱۱-۶۳۸I۲.۶,RP۱۱-۱۰۹D۲۰.۲ and RP۱۱-۳۴۲H۲۱.۲.Conclusion: Our results revealed many unannotated LncRNAs that might be crucial in progressand/or prognosis of colorectal cancer. We speculate that RP۱۱-۶۳۸I۲.۶, RP۱۱-۱۰۹D۲۰.۲ andRP۱۱-۳۴۲H۲۱.۲ may have key roles in biological pathways related to RNA editing due to theirtight association with APOBEC۳A. Further functional analysis is required for clarifying thepotential roles of these candidate LncRNAs as potential diagnostic markers or druggable targetsin CRC.

کلیدواژه ها:

Colorectal cancer ، Diagnostic biomarkers ، Transcriptome analysis ، Differential expression ، Long non-coding RNAs