Identification of AP002498.1 and LINC01871 as prognostic biomarkers and therapeutic targets for distant metastasis of colorectal adenocarcinoma

Abstract

AbstractBackgroundIncreasing evidence suggests that lncRNA (Long non‐coding RNA, lncRNA)‐mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA–miRNA–mRNA ceRNA network in distant metastasis of CRC are still unclear.MethodsIn this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA‐Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT–PCR and univariate and multivariate analysis of the metastasis‐ and prognosis‐related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC.ResultsTwo key distant metastasis‐related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA‐associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1‐ and LINC01871‐associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs.ConclusionThe DElncRNA AP002498.1 and the LINC01871/miR‐4644 and miR‐185‐5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.