Construction and Validation of a Prognostic Nomogram for Lung Adenocarcinoma Based on a m6A RNA Methylation Regulator-Related Signature

2020 ◽  
Author(s):  
Xiao Wu ◽  
Hongxu Sheng ◽  
Pinghui Xia ◽  
Yiqing Wang ◽  
Li Yu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Rna Methylation ◽  
M6a Rna Methylation

scholarly journals Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 619
Author(s):  
Xiuhong Li ◽  
Zian Feng ◽  
Rui Wang ◽  
Jie Hu ◽  
Xiaodong He ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
Kaplan Meier ◽  
M6a Rna Methylation ◽  
Prediction Efficiency

N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m6A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m6A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m6A methylation regulators in LUAD.

scholarly journals Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Zhou ◽  
Miaosen Zheng ◽  
Muqi Shi ◽  
Jinjie Wang ◽  
Zhanghao Huang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Prognostic Model ◽  
Immune Cell ◽  
Immune Cell Infiltration ◽  
Immune Microenvironment ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky. Methods The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model. Result Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094). Conclusion Our study provides a robust signature for predicting patients’ prognosis, which might be helpful for therapeutic strategies discovery of LUAD.

scholarly journals Development and validation of m6A RNA methylation regulators-based signature in lung adenocarcinoma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Wei Guo ◽  
Qi-Lin Huai ◽  
Si-Jin Sun ◽  
Lei Guo ◽  
Xue-Min Xue ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Development And Validation

scholarly journals Construction of a m6A RNA Methylation Regulator-related Signature for Prognosis and Immune Response in Lung Adenocarcinoma

2020 ◽  
Author(s):  
Xiao Wu ◽  
Hongxu Sheng ◽  
Pinghui Xia ◽  
Yiqing Wang ◽  
Li Yu ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Survival Prediction ◽  
Hub Genes ◽  
Rna Methylation ◽  
High Risk Patients ◽  
Cancer Pathogenesis ◽  
Risk Patients ◽  
Regulator Genes ◽  
M6a Rna Methylation

Abstract BackgroundN6-methyladenosine (m6A) RNA methylation is related to cancer pathogenesis and development. However, few studies have investigated the role of m6A regulator genes in lung adenocarcinoma (ADC).MethodsGene expressions with clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) database. We compared the expression of twenty m6A regulator genes between tumor and normal samples. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression model were used to derive a multi-gene signature. A signature-based nomogram was developed, and the prediction performance was validated by an exterior validation set (GSE72094). Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network and identify the hub genes. The association of m6A signature with immunity was examined.ResultsSeventeen differentially expressed genes were identified. A five-gene prognostic signature (IGF2BP1, IGF2BP2, HNRNPA2B1, METTL3, and HNRNPC) was determined, and demonstrated as an unfavorable prognostic factor. A signature-based nomogram was developed to predict each patient’s survival probability, and the nomogram was well calibrated and showed a satisfactory discrimination. Turquoise was identified as the most risk-related module, and genes in this module were enriched in the pathway of cell cycle. Six genes were determined as the hub genes. High-risk patients had significantly higher expression of PD-L1, higher tumor mutational burden (TMB), higher proportion of immune checkpoint blockade (ICB) response, and lower proportion of T cells CD8.ConclusionsIn summary, the signature-based nomogram is useful for survival prediction, and high-risk patients were more sensitive to the ICB therapy.

scholarly journals Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-related Genes and Construction of the Risk Score for Prognostication in Early-stage Lung Adenocarcinoma

2020 ◽  
Author(s):  
Bingzhou Guo ◽  
Hongliang Zhang ◽  
Jinliang Wang ◽  
Rilige Wu ◽  
Junyan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Early Stage ◽  
Gene Signature ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Cox Analysis ◽  
Random Survival Forest

Abstract Background: N6-methyladenosine (m6A) RNA modification play critical roles in tumorigenesis because it can change gene expression and even the function in multiple levels including the regulation of degradation, subcellular localization, splicing and local conformation changes of RNA transcripts. In this study, we aim to conduct comprehensive investigation on m6A RNA methylation regulators and m6A-related genes and their association with prognosis in early-stage Lung adenocarcinoma (LUAD). Methods: The relevant datasets which were used to analyze 21 m6A RNA methylation regulators and 887 m6A-related genes in m6Avar were downloaded from Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate cox regression analysis, random survival forest analysis, Kaplan-Meier anylysis, STRING and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on five feature genes was constructed.Results: Respectively, we treated GSE31210 (n=226) as training set, GSE50081 (n=128) and TCGA data (n=461) as test set. By performing univariable cox regression and random survival forest algorithm in the training group, five prognosis-related genes including DENND1A, KBTBD6, KIF4A, BMPER, and YTHDC2 were screened out, which could divide LUAD patients into low-risk group and high-risk group (log rank P < 0.001). The predictive efficacy of these genes was confirmed in the test group GSE50081 (log rank P < 0.01) and TCGA datasets (log rank P < 0.001). Cox analysis showed that this five-gene signature was an independent risk factor in LUAD. Further, genes in the signature were also external validated using online database. YTHDC2 played vital role of readers in m6A methylation.Conclusion: The findings of this study suggested that associated with m6A-related genes and m6A RNA methylation regulators, five-gene signature was reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.

scholarly journals Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma

2021 ◽  
Author(s):  
Bingzhou Guo ◽  
Hongliang Zhang ◽  
Jinliang Wang ◽  
Rilige Wu ◽  
Junyan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Early Stage ◽  
Gene Signature ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Cox Analysis ◽  
Random Survival Forest

Abstract BackgroundN6-methyladenosine (m6A) RNA modification play critical roles in tumorigenesis because it can change gene expression and even the function in multiple levels including the regulation of degradation, subcellular localization, splicing and local conformation changes of RNA transcripts. In this study, we aim to conduct comprehensive investigation on m6A RNA methylation regulators and m6A-related genes and their association with prognosis in early-stage Lung adenocarcinoma (LUAD). MethodsThe relevant datasets which were used to analyze 21 m6A RNA methylation regulators and 887 m6A-related genes in m6Avar were downloaded from Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate cox regression analysis, random survival forest analysis, Kaplan-Meier anylysis, STRING and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on five feature genes was constructed.ResultsRespectively, we treated GSE31210 (n=226) as training set, GSE50081 (n=128) and TCGA data (n=461) as test set. By performing univariable cox regression and random survival forest algorithm in the training group, five prognosis-related genes including DENND1A, KBTBD6, KIF4A, BMPER, and YTHDC2 were screened out, which could divide LUAD patients into low-risk group and high-risk group (log rank P < 0.001). The predictive efficacy of these genes was confirmed in the test group GSE50081 (log rank P < 0.01) and TCGA datasets (log rank P < 0.001). Cox analysis showed that this five-gene signature was an independent risk factor in LUAD. Further, genes in the signature were also external validated using online database. YTHDC2 played vital role of readers in m6A methylation.ConclusionThe findings of this study suggested that associated with m6A-related genes and m6A RNA methylation regulators, five-gene signature was reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.

scholarly journals Identification of the Signature Associated with m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma

2020 ◽  
Author(s):  
Bingzhou Guo ◽  
Hongliang Zhang ◽  
Jinliang Wang ◽  
Rilige Wu ◽  
Junyan Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Early Stage ◽  
Gene Signature ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
Cox Analysis ◽  
Random Survival Forest

Abstract Background: N6-methyladenosine (m6A) RNA modification play critical roles in multiple levels including the regulation of degradation, subcellular localization, splicing and local conformation changes of RNA transcripts. In this study, we aim to conduct comprehensive investigation on m6A RNA methylation regulators and m6A-related genes and their association with prognosis in early-stage Lung adenocarcinoma (LUAD). Methods: The relevant datasets which were used to analyze 21 m6A RNA methylation regulators and 887 m6A-related genes in m6Avar were downloaded from Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate cox regression analysis, random survival forest analysis, Kaplan-Meier anylysis, STRING and multivariate cox analysis were carried out, and a risk prognostic model based on five feature genes was constructed. Respectively, we treated GSE31210 (n=226) as training set, GSE50081 (n=128) and TCGA data (n=461) as test set. Results: By performing univariable cox regression and random survival forest algorithm in the training group, five prognosis-related genes including DENND1A, KBTBD6, KIF4A, BMPER, and YTHDC2 were screened out, which could divide LUAD patients into low-risk group and high-risk group (log rank p <0.001). The predictive efficacy of these genes was confirmed in the test group GSE50081 (log rank p <0.01) and TCGA datasets (log rank p <0.001). Cox analysis showed that this five-gene signature was an independent risk factor in LUAD. Further, genes in the signature were also external validated using online database. YTHDC2 played vital role of readers in m6A methylation. Conclusions: The findings of this study suggested that associated with m6A-related genes and m6A RNA methylation regulators, five-gene signature was reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target.

scholarly journals The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mohammad Burhan Uddin ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Noncoding Rna ◽  
Rna Modification ◽  
Oncogenic Signaling ◽  
Aberrant Expression ◽  
Rna Methylation ◽  
Rna Molecules ◽  
M6a Rna Methylation ◽  
Oncogenic Signaling Pathways

AbstractThe m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

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