Dataset Information

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients.

ABSTRACT:

Background

Colon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.

Materials and methods

The m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.

Results

We identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.

Conclusion

In this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.

SUBMITTER: Zhang P

PROVIDER: S-EPMC8321625 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive, fatal tumor. N6-methylandenosine (m6A) methylation is the major epigenetic modification of RNA including lncRNAs. The roles of m6A-related lncRNAs in PDAC have not been fully clarified. This study aims to assess gene signatures and prognostic value of m6A-related lncRNAs in PDAC. The Cancer Genome Atlas (TCGA) dataset and the International Cancer Genome Consortium (ICGC) dataset were explored to identify m6A-related lncRNAs. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were performed to construct the m6A-related lncRNAs prognostic riskscore (m6A-LPR) model to predict the overall survival (OS) in the TCGA training cohort. Kaplan-Meier curve with log-rank test and receiver operating characteristic (ROC) curve were used to evaluate the prognostic value of the m6A-LPR. Furthermore, the robustness of the m6A-LPR was further validated in the ICGC cohort. Tumor immunity was evaluated using ESTIMATE and CIBERSORT algorithms. A total of 262 m6A-related lncRNAs were identified in two datasets. In the TCGA training cohort, 28 prognostic m6A-related lncRNAs were identified and the m6A-LPR including four m6A-related lncRNAs was constructed. The m6A-LPR was able to identify high-risk patients with significantly poorer OS and accurately predict OS in both the TCGA training cohort and the ICGC validation cohort. Analysis of tumor immunity revealed that high-risk groups had remarkably lower stromal, immune, and ESTIMATE scores. Moreover, high-risk groups were associated with significantly higher levels of plasma B cells and resting NK cells infiltration, and lower levels of infiltrating resting memory CD4 T cells, monocytes, and resting mast cells. Our study proposed a robust m6A-related prognostic signature of lncRNAs for predicting OS in PDAC, which provides some clues for further studies focusing on the mechanism process underlying m6A modification of lncRNAs.

Project description:BackgroundColon adenocarcinoma (COAD) is the most common colon cancer exhibiting high mortality. Due to their association with cancer progression, long noncoding RNAs (lncRNAs) are now being used as prognostic biomarkers. In the present study, we used relevant clinical information and expression profiles of lncRNAs originating from The Cancer Genome Atlas database, aiming to construct a prognostic lncRNA signature to estimate the prognosis of patients.MethodsThe samples were randomly spilt into training and validation cohorts. In the training cohort, prognosis-related lncRNAs were selected from differentially expressed lncRNAs using the univariate Cox analysis. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were employed for identifying prognostic lncRNAs. The prognostic signature was constructed by these lncRNAs.ResultsThe prognostic model was able to calculate each COAD patient's risk score and split the patients into groups of low and high risks. Compared to the low-risk group, the high-risk group had significant poor prognosis. Next, the prognostic signature was validated in the validation, as well as all cohorts. The receiver operating characteristic (ROC) curve and c-index were determined in all cohorts. Moreover, these prognostic lncRNA signatures were combined with clinicopathological risk factors to construct a nomogram for predicting the prognosis of COAD in the clinic. Finally, seven lncRNAs (CTC-273B12.10, AC009404.2, AC073283.7, RP11-167H9.4, AC007879.7, RP4-816N1.7, and RP11-400N13.2) were identified and validated by different cohorts. The Kyoto Encyclopedia of Genes and Genomes analysis of the mRNAs co-expressed with the seven prognostic lncRNAs suggested four significantly upregulated pathways, which were AGE-RAGE, focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways.ConclusionThus, our study verified that the seven lncRNAs mentioned can be used as biomarkers to predict the prognosis of COAD patients and design personalized treatments.