Screening key lncRNAs and mRNAs for left-sided and right-sided colon adenocarcinoma based on lncRNA-mRNA functional synergistic network

Transl Cancer Res. 2020 Apr;9(4):2312-2325. doi: 10.21037/tcr.2020.03.29.

Abstract

Background: The difference between right-sided colon adenocarcinoma (RSCOAD) and left-sided colon adenocarcinoma (LSCOAD) patients has been a controversial issue. The purpose of this study was to screen key lncRNAs and mRNAs in RSCOAD and LSCOAD.

Methods: We used The Cancer Genome Atlas (TCGA) data to screen differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). The optimal diagnostic lncRNA biomarkers for RSCOAD and LSCOAD were identified using Boruta algorithm. DEmRNA-DElncRNA interaction analysis was constructed. DEmRNAs co-expressed with DElncRNAs were functionally annotated. The expression of selected DElncRNAs and DEmRNAs were verified by qRT-PCR.

Results: A total of 2,672 DEmRNAs (1,050 down-regulated and 1,622 up-regulated mRNAs) and 453 DElncRNAs (139 down-regulated and 314 up-regulated lncRNAs) between RSCOAD and LSCOAD were identified. We also obtained 31 optimal diagnostic lncRNAs biomarkers in RSCOAD compared to LSCOAD. The AUC of the random forests model was 0.902 and the specificity and sensitivity of this model were 83.5% and 82.1%, respectively. Three DElncRNAs (HAGLR, HOXB-AS3 and SATB2-AS1) and three DEmRNAs (HOXD1, HOXB3 and SATB2) were identified as key DElncRNAs and DEmRNAs, respectively. Age, residual tumor, stage, and M were independent predictors of survival. The qRT-PCR analysis were consistent with our TCGA integration analysis, generally.

Conclusions: HOXD1, HOXB3 and SATB2, HAGLR, HOXB-AS3 and SATB2-AS1 may be involved in the pathogenesis of RSCOAD and LSCOAD, and may contribute to the understanding of the pathological mechanism of RSCOAD and LSCOAD.

Keywords: DElncRNAs-DEmRNAs co-expression; Right-sided colon adenocarcinoma (RSCOAD); The Cancer Genome Atlas (TCGA); differentially expressed lncRNAs (DElncRNAs); differentially expressed mRNAs (DEmRNAs); left-sided colon adenocarcinoma (LSCOAD).