Identification and Validation of an m6A-Related LncRNA Signature to Predict Progression-Free Survival in Colorectal Cancer

Abstract

The RNA methylation of N6 adenosine (m6A) plays a crucial role in various biological processes. Strong evidence reveals that the dysregulation of long non-coding RNAs (lncRNA) brings about the abnormality of downstream signaling in multiple ways, thus influencing tumor initiation and progression. Currently, it is essential to discover effective and succinct molecular biomarkers for predicting colorectal cancer (CRC) prognosis. However, the prognostic value of m6A-related lncRNAs for CRC remains unclear, especially for progression-free survival (PFS). Here, we screened 24 m6A-related lncRNAs in 622 CRC patients and identified five lncRNAs (SLCO4A1-AS1, MELTF-AS1, SH3PXD2A-AS1, H19 and PCAT6) associated with patient PFS. Compared to normal samples, their expression was up-regulated in CRC tumors from TCGA dataset, which was validated in 55 CRC patients from our in-house cohort. We established an m6A-Lnc signature for predicting patient PFS, which was an independent prognostic factor by classification analysis of clinicopathologic features. Moreover, the signature was validated in 1,077 patients from six independent datasets (GSE17538, GSE39582, GSE33113, GSE31595, GSE29621, and GSE17536), and it showed better performance than three known lncRNA signatures for predicting PFS. In summary, our study demonstrates that the m6A-Lnc signature is a promising biomarker for forecasting patient PFS in CRC.