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

doi:10.3870/j.issn.1672-8009.2026.02.012

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (2): 194-203.doi: 10.3870/j.issn.1672-8009.2026.02.012

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

黄启昌¹, 何雨霖¹, 钟金俞², 周韶璋^3Δ, 谭莉萍^3Δ

广西医科大学¹肿瘤医学院,²第二临床医学院南宁市,530021
³广西医科大学附属肿瘤医院呼吸肿瘤内科南宁市,530201

收稿日期:2025-04-08 出版日期:2026-03-31 发布日期:2026-04-03
通讯作者: 周韶璋(E-mail:Zhoushaozhang@gxmu.edu.cn),谭莉萍(E-mail:988tan@163.com)
Δ:共同通信作者
基金资助:
广西自然科学基金面上项目(No.2024GXNSFAA010404、No.SLB-2-20250317-89)

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

HUANG Qichang¹, HE Yulin¹, ZHONG Jinyu², ZHOU Shaozhang^3Δ, TAN Liping^3Δ

¹College of Oncology,²The Second Clinical College of Medicine,Guangxi Medical University,Nanning,530021,China
³Department of Respiratory Oncology,Tumor Hospital Affiliated to Guangxi Medical University,Nanning,530201,China

Received:2025-04-08 Online:2026-03-31 Published:2026-04-03
Contact: ZHOU Shaozhang(E-mail:Zhoushaozhang@gxmu.edu.cn),TAN Liping(E-mail:988tan@163.com)
Δ:These author contributed equally as corresponding authors
Supported by:
General Project of Natural Science Foundation of Guangxi Province(No.2024GXNSFAA010404,No.SLB-2-20250317-89)

摘要/Abstract

摘要： 目的构建肺腺癌(lung adenocarcinoma,LUAD)与肺鳞癌(lung squamous cell carcinoma,LUSC)的铁死亡相关基因预后模型,比较二者分子通路、免疫及表观遗传特征差异,探索免疫检查点与m6A因子调控铁死亡的机制。方法基于TCGA数据和FerrDb基因集,经差异表达分析、COX及LASSO回归建模;通过Kaplan-Meier法和ROC曲线评估模型性能;结合GSEA分析与文献筛选差异基因(P<0.001)并提出假说。结果 LUAD预后模型(CYBB、GLS2、CAV1、DDIT4、SLC7A5、TRIB3、IL33、RRM2)1、3、5年AUC分别为0.720、0.690、0.640(P<0.001),LUSC预后模型(ALOX5、MIOX、JUN、SLC7A5、ARRDC3)AUC分别为0.608、0.637、0.652(P=0.003),优于现有模型,风险得分为独立预后因子(P<0.05)。LUAD富集蛋白酶体、TCA循环,LUSC富集白细胞迁移、黏着斑(P<0.05);LUAD的TNFSF18、METTL3低表达,LUSC的NRP1、FTO高表达(P<0.001)。由此提出以下机制假说:LUSC中CD28影响铁死亡敏感性,FTO/YTHDF2驱动抵抗;LUAD中TNFSF18削弱GPX4抑制,存在双向调控网络。结论研究成功构建高效预后模型,多维度揭示两亚型本质差异,为铁死亡协同机制研究提供关键靶点与理论框架,为后续实验验证提供理论基础。

关键词: 肺腺癌, 肺鳞癌, 铁死亡, 预后模型, 免疫检查点, N6-甲基腺苷

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

中图分类号:

R734.2

黄启昌, 何雨霖, 钟金俞, 周韶璋, 谭莉萍. 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[J]. 医学分子生物学杂志, 2026, 23(2): 194-203.

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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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

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

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