N6-Methyladenosine-Related lncRNA Signature Predicts the Overall Survival of Colorectal Cancer Patients

Abstract

Background: The N6-methyladenosine (m6A) RNA modification can modify long non-coding RNAs (lncRNAs), thereby affecting the tumorigenesis and progression of tumors. However, the underlying role of m6A-modified lncRNAs in colorectal cancer (CRC) remains largely unknown. Therefore, our aim was to assess the prognostic value of m6A-modified lncRNAs in CRC patients. Methods: The gene expression and clinicopathological data of CRC were extracted from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to investigate the m6A-modified lncRNAs. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance of molecular subtypes was identified. The least absolute shrinkage and selection operator analysis (LASSO) was applied to establish a risk signature. Finally, a prognostic nomogram with risk score and clinicopathological variables was established. Results: In total, 29 m6A-modified lncRNAs were identified as prognostic lncRNAs. Two molecular clusters were identified and significant differences were found with respect to clinicopathological features and prognosis. Cluster1 is associated with poor overall survival (OS), down-regulation of Programmed cell death ligand-1 (PD-L1) expression, lower immune score, and less immune cell infiltration. Then, an m6A-modified lncRNA signature for predicting OS was constructed in the TCGA training cohort. The signature demonstrated favorable prediction performance in both training and validation sets. Compared with low-risk patients, patients with high risk showed worse clinical outcomes, lower immune scores, and downregulated PD-L1 expression. Further analysis indicated that the signature was an independent prognostic indicator, and then a prognostic nomogram based on risk score, tumor location, and tumor stage was established. Conclusions: Our study identified a seven m6A-modified lncRNA signature and established a prognostic nomogram that reliably predicts OS in CRC. These findings may improve the understanding of m6A modifications in CRC and provide insights into the prognosis and treatment strategy of CRC.

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer

“…Nonetheless, the outcome is highly heterogeneous in patient subgroup with different tumor microenvironment ( Zeng et al, 2021 ). The tumor microenvironment has been demonstrated to affect the result of immunotherapy in various studies ( Song et al, 2021 ). According to the immune cell infiltration in tumor microenvironment, the tumor is classified into two types: “hot tumor” and “cold tumor” ( Zhao et al, 2021 ).…”

Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer

“…Accumulated evidence showed that m6A modi cation by targeting downstream genes played a considerable role in tumor proliferation, differentiation, development, invasion, and metastasis (Xu et al 2021, Hua et al 2018, Liu et al 2018. Accumulated evidence reveled that m6A regulators and their targets may play a crucial role in the bene t of immunotherapy (Cong et al 2021, Song et al 2021). Yet, the studies to date have tended to focus on m6A regulators rather than their targets and far too little attention has been paid to the potential role of m6A regulators and their targets in uencing ovarian cancer immunotherapy.…”

A novel fatty acid metabolism‐related gene signature predicts the prognosis, tumor immune properties, and immunotherapy response of colon adenocarcinoma patients

“…Additionally, Zhang et al created a predictive signature based on 6‐carbon metabolism and TCA‐related mRNAs to predict 1‐year OS in COAD 43 . In another study by Song et al, they discovered a signature for evaluating the 3‐ and 5‐ year survival probability in CRC patients utilizing seven m6A‐modified lncRNAs 44 . One, 3, and 5‐year OS AUCs of 0.66, 0.66, and 0.67 were found in a study by Chen et al 41 However, in research by Yang et al, 42 the AUCs of OS for the same years were 0.7632, 0.7411, and 0.7581, respectively.…”

“…43 In another study by Song et al, they discovered a signature for evaluating the 3-and 5-year survival probability in CRC patients utilizing seven m6A-modified lncRNAs. 44 One, 3, and 5-year OS AUCs of 0.66, 0.66, and 0.67 were found in a study by Chen et al 41 However, in research by Yang et al, 42 the AUCs of OS for the same years were 0.7632, 0.7411, and 0.7581, respectively. Compared to the AUCs in this training set (0.726, 0.687, and 0.748) and pooled set (0.813, 0.691, and 0.795) of the present study, Chen's research had reduced AUCs.…”