Construction of Prognostic Model and Comparison of Subtype Characteristics of Non-Small Cell Lung Cancer Based on Ferroptosis-Related Genes

doi:10.3870/j.issn.1672-8009.2026.02.012

Abstract

Abstract: Objective To construct a prognostic model for iron death related genes in lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),compare the differences in molecular pathways,immunity and epigenetic characteristics between the two,and explore the mechanisms of immune checkpoints and m6A factors regulating iron death.Methods Based on the TCGA data and the FerrDb gene set,the models were constructed after differential expression analysis,COX regression,and LASSO regression.The model performance was evaluated using the Kaplan-Meier method and ROC curves.The differentially expressed genes(P<0.001)were analyzed by GSEA and literature screening,and the hypotheses were proposed.Results The LUAD prognostic model(CYBB,GLS2,CAV1,DDIT4,SLC7A5,TRIB3,IL33,RRM2)had the AUC of 0.720,0.690,and 0.640 for 1,3,and 5 years respectively(P<0.001),while the LUSC prognostic model(ALOX5,MIOX,JUN,SLC7A5,ARRDC3)had the AUC of 0.608,0.637,and 0.652 respectively(P=0.003),which was superior to existing models.The risk score was an independent prognostic factor(P<0.05).LUAD enriched in the pathways of proteasome and TCA cycle,while LUSC enriched in pathways of leukocyte migration and focal adhesion(P<0.05).In addition,LUAD showed low expression of TNFSF18 and METTL3,while LUSC showed high expression of NRP1 and FTO(P<0.001).Therefore,the mechanism hypothesis was proposed:In LUSC,CD28 affected iron death sensitivity,and FTO/YTHDF2 drived resistance;in LUAD,TNFSF18 weakened the inhibition of GPX4,and there was a bidirectional regulatory network.Conclusion By construction of the highly efficient prognostic models and analysis of the essential differences between the two subtypes from multiple dimensions,the key targets and theoretical frameworks for the study of the synergistic mechanism of iron death is therefore provided for the subsequent experimental verification.

Key words: lung adenocarcinoma, lung squamous cell carcinoma, ferroptosis, prognostic model, immune checkpoints, N6-methyladenosine

CLC Number:

R734.2

HUANG Qichang, HE Yulin, ZHONG Jinyu, ZHOU Shaozhang, TAN Liping. Construction of Prognostic Model and Comparison of Subtype Characteristics of Non-Small Cell Lung Cancer Based on Ferroptosis-Related Genes[J]. Journal of Medical Molecular Biology, 2026, 23(2): 194-203.

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