基于铁死亡相关基因的非小细胞肺癌预后模型构建及亚型特征比较OA

Objective To construct a prognostic model for iron death related genes in lung ade-nocarcinoma(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 analy-sis,COX regression,and LASSO regression.The model performance was evaluated using the Kap-lan-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 prognos-tic 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 ex-pression 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,TN-FSF18 weakened the inhibition of GPX4,and there was a bidirectional regulatory net-work.Conclusion By construction of the highly efficient prognostic models and analysis of the es-sential differences between the two subtypes from multiple dimensions,the key targets and theoreti-cal frameworks for the study of the synergistic mechanism of iron death is therefore provided for the subsequent experimental verification.