Upregulation of LncRNAs G2E3-AS1 and BACE1-AS as Prognostic Biomarkers in Metastatic Colorectal Cancer.

Abstract

Background: Despite the current diagnostic techniques and therapeutic methods for colorectal cancer (CRC), patients are often diagnosed at advanced stages of colorectal cancer with poor prognosis and distant metastasis. Recently, numerous investigations have highlighted the crucial role of lncRNAs in cancer development, progression, invasion, and metastasis. This study investigated less well-characterized genes in the colorectal cancer metastasis process using bioinformatics analysis and their confirmation by experimental methods.

Materials and methods: Genes expression profiles from colorectal cancer patients were downloaded from the TCGA database by the TCGAbiolinks R package. Differential gene expression analysis of miRNA, lncRNAs, and mRNAs was conducted for the M1 (metastatic) and M0 (non-metastatic) samples compared to control samples. Then, the DIANA lncbase3 tool was used to find M1-specific miRNA-LncRNA interactions. In addition, the expression of selected genes was evaluated by Real-time RT-PCR in forty-one CRC tissues (also normal adjacent tissues) to confirm the bioinformatics data.

Results: Our analysis showed that the expression levels of 77 lncRNAs, 12 miRNAs, and 627 mRNA were significantly changed only in metastatic tumors compared to control. In experimental study, significant overexpression of LncRNAs LINC00839, LINC01006, BACE1-AS and G2E3-AS1 was confirmed in metastatic tumors compared to control. Also, ROC analysis showed that these lncRNAs, especially lncRNAs G2E3-AS1 and BACE1-AS, are good prognostic biomarkers for metastatic colorectal tumors.

Conclusion: In conclusion, we demonstrated that the lncRNAs G2E3-AS1 and BACE1-AS expression upregulated in CRC tissues can be good potential biomarkers for metastatic colorectal cancer with poor prognostic.