1.Construction and Analysis of a Prognostic Risk Model for Lung Adenocarcinoma Based on m6A-related Genes
Meng FANG ; Fan YANG ; Nongyan WANG
Journal of Medical Research 2025;54(5):129-135
Objective To construct a prognostic model for lung adenocarcinoma(LUAD)based on N6-methyladenosine(m6A)-related genes and explore its clinical significance.Methods The LUAD dataset was obtained from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO).The TCGA dataset was divided into a training set and a validation set in a 7∶3 ratio.In the training set,the m6A-related gene prognostic model was constructed using univariate COX analysis and LASSO regression analysis.Risk scores were calculated for the TCGA,GSE30219,GSE31210,GSE41271,GSE50081,and GSE68465datasets.Patients were categorized into low-risk and high-risk groups based on the median value of the risk scores.Kaplan-Meier(KM)curves,receiver operating char-acteristic(ROC)curves and multivariate COX regression analysis were used to verify the reliability of the prognosis model.A nomogram model was constructed to assess the role of risk scores in prognostic monitoring.Gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways in the prognostic model.The correlation between risk scores,immune infiltration,and driver gene mutations was analyzed.Results A prognostic model comprising nine m6A-related genes(AKAP12,CBFA2T3,KIF14,KL,KRT6A,LIFR,MIF,RRM2,TLR8)was developed.which emerged as an independent prognostic factor for LUAD.The model based on the risk score,T stages and N stages,accurately predicted LUAD prognosis.In high-risk group,mTORC1,Myc signaling pathways,and DNA repair mechanisms were significantly activated,the infiltration of CD8+T cells and CD4+T cells decreased,the expression of CD276 in-creased,and the expression of CTLA4 decreased.Additionally,risk scores were correlated with EGFR and KRAS mutations.Conclusion The prognostic model based on m6A-related genes effectively predicts LUAD prognosis and can guide targeted therapy and immunothera-py treatments for patients.
2.Construction and Validation of A Prognostic Model of Lung Adenocarcinoma Based on m5C Modification-Related Genes
Fan YANG ; Nongyan WANG ; Meng FANG ; Yingjiao ZHANG ; Haiyan HU ; Peng FANG
Cancer Research on Prevention and Treatment 2025;52(3):208-216
Objective To construct a prognostic model of lung adenocarcinoma(LUAD)based on m5C modification-related genes and to explore its clinical value.Methods Based on the LUAD data in TCGA,GSE30219,GSE31210,and GSE50081 cohorts,prognosis-related m5C modification-related genes were screened,and the prognostic model was constructed by using univariate Cox,Lasso,and multivariate Cox regression analyses.Kaplan-Meier curve,ROC curve,and Cox regression were used to observe the robustness and prognostic performance of the model.The correlation between the prognostic model and clinico-pathologic features was further explored.Results A prognostic model consisting of eight m5C modifi-cation-related genes,including CDK1,CDKN1A,NOP2,RRM2,TCL6,TLR8,TRDMT1,and YTHDF2,was constructed.Risk score was an independent risk factor for the prognosis of patients with LUAD,and it is combined with age,T stage,and N stage to constitute a nomogram which can accurately predict the prognosis of patients.The infiltration of macrophages and CD4+/CD8+T cells was significantly reduced in high-risk patients.The risk score in LUAD tissues was significantly higher than that in normal tissues and was positively correlated with T stage and N stage.The risk score of smoking and EGFR wild-type patients was higher than that of non-smoking and EGFR-mutant patients.Conclusion The prognostic model constructed based on m5C modification-related genes has shown good accuracy and stability in predicting the prognosis of patients with LUAD,and it is closely related to clinical features,driver gene mutations,and immune infiltration,which can provide a potential basis for the treatment and prognostic assessment of LUAD.
3.Construction and Analysis of a Prognostic Risk Model for Lung Adenocarcinoma Based on m6A-related Genes
Meng FANG ; Fan YANG ; Nongyan WANG
Journal of Medical Research 2025;54(5):129-135
Objective To construct a prognostic model for lung adenocarcinoma(LUAD)based on N6-methyladenosine(m6A)-related genes and explore its clinical significance.Methods The LUAD dataset was obtained from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO).The TCGA dataset was divided into a training set and a validation set in a 7∶3 ratio.In the training set,the m6A-related gene prognostic model was constructed using univariate COX analysis and LASSO regression analysis.Risk scores were calculated for the TCGA,GSE30219,GSE31210,GSE41271,GSE50081,and GSE68465datasets.Patients were categorized into low-risk and high-risk groups based on the median value of the risk scores.Kaplan-Meier(KM)curves,receiver operating char-acteristic(ROC)curves and multivariate COX regression analysis were used to verify the reliability of the prognosis model.A nomogram model was constructed to assess the role of risk scores in prognostic monitoring.Gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways in the prognostic model.The correlation between risk scores,immune infiltration,and driver gene mutations was analyzed.Results A prognostic model comprising nine m6A-related genes(AKAP12,CBFA2T3,KIF14,KL,KRT6A,LIFR,MIF,RRM2,TLR8)was developed.which emerged as an independent prognostic factor for LUAD.The model based on the risk score,T stages and N stages,accurately predicted LUAD prognosis.In high-risk group,mTORC1,Myc signaling pathways,and DNA repair mechanisms were significantly activated,the infiltration of CD8+T cells and CD4+T cells decreased,the expression of CD276 in-creased,and the expression of CTLA4 decreased.Additionally,risk scores were correlated with EGFR and KRAS mutations.Conclusion The prognostic model based on m6A-related genes effectively predicts LUAD prognosis and can guide targeted therapy and immunothera-py treatments for patients.
4.Construction and Validation of A Prognostic Model of Lung Adenocarcinoma Based on m5C Modification-Related Genes
Fan YANG ; Nongyan WANG ; Meng FANG ; Yingjiao ZHANG ; Haiyan HU ; Peng FANG
Cancer Research on Prevention and Treatment 2025;52(3):208-216
Objective To construct a prognostic model of lung adenocarcinoma(LUAD)based on m5C modification-related genes and to explore its clinical value.Methods Based on the LUAD data in TCGA,GSE30219,GSE31210,and GSE50081 cohorts,prognosis-related m5C modification-related genes were screened,and the prognostic model was constructed by using univariate Cox,Lasso,and multivariate Cox regression analyses.Kaplan-Meier curve,ROC curve,and Cox regression were used to observe the robustness and prognostic performance of the model.The correlation between the prognostic model and clinico-pathologic features was further explored.Results A prognostic model consisting of eight m5C modifi-cation-related genes,including CDK1,CDKN1A,NOP2,RRM2,TCL6,TLR8,TRDMT1,and YTHDF2,was constructed.Risk score was an independent risk factor for the prognosis of patients with LUAD,and it is combined with age,T stage,and N stage to constitute a nomogram which can accurately predict the prognosis of patients.The infiltration of macrophages and CD4+/CD8+T cells was significantly reduced in high-risk patients.The risk score in LUAD tissues was significantly higher than that in normal tissues and was positively correlated with T stage and N stage.The risk score of smoking and EGFR wild-type patients was higher than that of non-smoking and EGFR-mutant patients.Conclusion The prognostic model constructed based on m5C modification-related genes has shown good accuracy and stability in predicting the prognosis of patients with LUAD,and it is closely related to clinical features,driver gene mutations,and immune infiltration,which can provide a potential basis for the treatment and prognostic assessment of LUAD.

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