Comprehensive Analysis Of Prognostic Models Of Ferroptosis-related LncRNAs In Lung Adenocarcinoma

Lung cancer is a malignant tumor originating from the bronchial mucosa or glands of the lungs,with high morbidity and mortality,and is one of the most threatening malignant tumors to human health and life.In the past 50 years,many countries have reported that the morbidity and mortality of lung cancer have increased significantly.The incidence and mortality of lung cancer in men are the first of all malignant tumors,and the incidence and mortality of women are the second.Its incidence has continued to increase in recent years.Finding new prognostic indicators for lung cancer treatment is one of the major issues in lung cancer research.Different from apoptosis,necrosis,pyroptosis and autophagy,ferroptosis is an iron-dependent lipid reactive oxygen species pathway.The main mechanism is that Fe²⁺transfers electrons to the oxygen atoms in the cells,and the oxygen atoms generate ROS,so that the phospholipid molecules in the long-chain unsaturated fatty acids on the cell membrane or organelle membrane are peroxidized to generate lipid peroxides,which in turn cause the formation of lipid peroxides.The thinning and increased curvature of the biofilm causes cell membrane rupture and cell death.Long non-coding RNAs（lncRNAs）are RNAs with a length of more than 200nucleotides.Their evolutionary conservation and expression are low,and their protein-coding capacity is limited.However,recent studies have found that lncRNAs play a role in cancer pathogenesis,tumorigenesis,and blood vessels.important role in generation.Lnc RNAs are capable of regulating gene expression at different levels,including histone modification,transcriptional and post-transcriptional regulation,and can act as activators or guides of interacting proteins,DNA,and RNA.Growing evidence suggests that lncRNAs can play critical roles in nearly all biological processes,including stem cell maintenance,cell proliferation,apoptosis,cell invasion,and metastasis.The number of aberrantly expressed lncRNAs reported to be involved in the development of cancer continues to grow,and increasing evidence suggests that functional lncRNAs are promising biomarkers and potential targets for prognosis.Cancer development and progression coincides with changes in the surrounding stroma.Cancer cells can functionally construct their tumor microenvironment（TME）by secreting various cytokines,chemokines,etc.This leads to a regrouping of surrounding cells,enabling them to play a decisive role in tumor survival and progression.Immune cells are an important component of the tumor stroma and play a crucial role in this process.There is increasing evidence that innate immune cells（macrophages,neutrophils,dendritic cells,innate lymphocytes,myeloid-derived suppressor cells,and NK cells）and adaptive immune cells（T and B cells）present in the tumor microenvironment.In this study,we extracted ferroptosis genes based on The Cancer Genome Atlas（TCGA）and established a co-expression network of ferroptosis-related m RNAs and lncRNAs.Through univariate and multivariate Cox analysis,a ferroptosis-related lncRNA prognostic model was constructed.Fer RLSig is composed of 10 lncRNAs related to ferroptosis,namely AL606489.1,AC106047.1,LINC02081,AC090559.1,AC026355.1,FAM83A-AS1,AL034397.3,AC092171.5,AC010980.2 and AC123595.1.High-risk grouping of Fer RLSig was significantly associated with worse overall survival.ROC and PCA further verified the accuracy of the model,and the results showed that Fer RLSig had a good prediction effect.Next,we developed a nomogram for predicting survival by combining Fer RLSig with clinicopathological features,establishing an intuitive predictive survival software to predict the OS of patients.In addition,enrichment analysis（GSEA）revealed that Fer RLSig was involved in many immunoregulatory pathways associated with malignancy.Based on risk models,we found significant differences in immune status and responses to immunotherapy,chemotherapy,and targeted drug therapy between high-and low-risk groups.These results provide new insights into the pathogenesis of LUAD and may provide valuable information for immunological research and precision medicine treatment.