Potential Prognostic Value of a Seven m6A-Related LncRNAs Signature and the Correlative Immune Infiltration in Colon Adenocarcinoma

Abstract

Long non-coding RNAs (lncRNAs) and their N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis and cancer progression. This study was designed to explore the value of m6A-related lncRNAs in prognosis and therapeutic applications of immune infiltration of colon adenocarcinoma (COAD). We downloaded the COAD gene expression and clinical data from The Cancer Genome Atlas project. By co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression, we constructed an independent prognostic signature of seven m6A-related lncRNAs. The prognostic lncRNAs were divided into two clusters by consistent clustering analysis, as well as into two groups of low–high risk based on the signature. Then we identified the relationship between the different groups with clinical features and immune cell infiltration. Cluster 2 had a higher risk score with a lower survival rate. The risk score was higher in groups with advanced clinical features, such as stage III–IV, N1-3, and M1. The expression of AC156455.1 was increased in tumor tissues and cluster 2, and the lncRNA ZEB1−AS1 was notably higher in the high-risk group. Five types of immune cells showed differences in two clusters, and most were upregulated in type 2. The expression of memory B cells was positively correlated with the risk score. The prognostic model was verified by the Gene Expression Omnibus (GEO) dataset. Besides, we found that the expression of these seven lncRNAs in tumor tissues was significantly higher than that in normal tissues, which verified the feasibility of the model. Thus, the signature of seven m6A-related lncRNAs can independently predict the prognosis of COAD. This signature is also closely associated with immune cell infiltration, and new therapeutic targets can be explored from this field.

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer

“…In the overall cohort ( Figure 6G ), the RMlnc-score (our study) had an AUC of 0.737 at 5-years overall survival, which was substantially higher than ChaiLncSig (AUC = 0.653), YunLncSig (AUC = 0.658), and ZhangLncSig (AUC = 0.659). This suggests that the RMlnc-score has higher accuracy in predicting survival compared to three recently published lncRNA signatures for colon cancer ( Chai et al, 2021 ; Yun and Yang, 2021 ; Zhang et al, 2021d ). The survival status and RMlnc-score score curves for the training and test sets showed ( Figure 6H, I , 7I) that RMlnc-score was proportional to the number of deaths in CC patients.…”

N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma

“…With the advances in high-throughput sequencing technology, more and more studies have published different kinds of RNA modification including the internal mRNA m7G methylation. In clinical research, several previous studies identified the role of N6-methyladenosine (m6A) remodeling in the molecular pathogenesis of several types of carcinogenesis and the role of m6A-related genes in the prognosis of several types of cancers ( Chai et al, 2021 ; Jin et al, 2021 ; Han et al, 2022 ). M6A remodeling has been well studied in HCC as some studies have identified m6A related gene signature model for the prediction of HCC ( Jin et al, 2021 ; Wang et al, 2021 ).…”

In Silico Identification and Validation of Cuproptosis-Related LncRNA Signature as a Novel Prognostic Model and Immune Function Analysis in Colon Adenocarcinoma

“…The differences between the two groups were assessed using t -tests (for normally distributed data) or Mann–Whitney tests (for non-normal distribution), and p < 0.05 was considered statistically significant. The relationships between risk score and drug sensitivity were determined by the Spearman’s correlation analysis [ 14 ]. p values were two-sided and all data with p < 0.05 were recognized as statistically significant.…”

“…They play a key role in various cellular processes in the cancer disease process [ 11 , 12 , 13 ]. Numerous studies have shown that lncRNAs can be involved in colon adenocarcinoma progression and immunotherapy through various pathways, such as m6A [ 14 ], ferroptosis [ 15 ], necroptosis [ 16 ], and autophagy [ 17 ]. In contrast, the value of the cuproptosis-related lncRNA prognostic model in colon adenocarcinoma has not received attention.…”