A novel ferroptosis-related genes model for prognosis prediction of lung adenocarcinoma.

Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. This study aims to investigate the potential correlation between ferroptosis and the prognosis of lung adenocarcinoma (LUAD). RNA-seq data were collected from the LUAD dataset of The Cancer Genome Atlas (TCGA) database. Based on ferroptosis-related genes, differentially expressed genes (DEGs) between LUAD and paracancerous specimens were identified. The univariate Cox regression analysis was performed to screen key genes associated with the prognosis of LUAD. LUAD patients were divided into the training set and validation set. Then, we screened out key genes and built a prognostic prediction model involving 5 genes using the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation and the multivariate Cox regression analysis. After dividing LUAD patients based on the median level of risk score as cut-off value, the generated prognostic prediction model was validated in the validation set. Moreover, we analyzed the somatic mutations, and estimated the scores of immune infiltration in the high-risk and low-risk groups. Functional enrichment analysis of DEGs was performed as well. High-risk scores indicated the worse prognosis of LUAD. The maximum area under curve (AUC) of the training set and the validation set in this study was 0.7 and 0.69, respectively. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of LUAD cases with the survival time of 1, 3 and 5 years was 0.698, 0.71 and 0.73, respectively. In addition, the mutation frequency of LUAD patients in the high-risk group was significantly higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results. This study constructs a novel LUAD prognosis prediction model involving 5 ferroptosis-related genes, which can be used as a promising tool for decision-making of clinical therapeutic strategies of LUAD.

Li F ，Ge D ，Sun SL 《BMC Pulmonary Medicine》

A novel ferroptosis-related gene signature for prognostic prediction of patients with lung adenocarcinoma.

Jin J ，Liu C ，Yu S ，Cai L ，Sitrakiniaina A ，Gu R ，Li W ，Wu F ，Xue X ... -  《Aging-US》

[Construction and Validation of Prognostic Risk Score Model of Autophagy Related Genes in Lung Adenocarcinoma].

Zhou J ，Wang X ，Li Z ，Jiang R ... -  《-》

Construction and analysis of a novel ferroptosis-related gene signature predicting prognosis in lung adenocarcinoma.

Ferroptosis is a newly discovered, iron-dependent, nonapoptotic form of programmed cell death that plays an important role in the development of lung adenocarcinoma (LUAD). In this study, ferroptosis-related genes (FRGs) were identified from the FerrDb dataset, and the mRNA expression profiles and corresponding clinical data of LUAD patients were downloaded from the University of California, Santa Cruz (UCSC) databases. Data from LUAD patients from the Gene Expression Omnibus (GEO) dataset were used as the verification set. Cox and Lasso regression analyses were used to screen the FRGs with prognostic value, and six prognostic-related FRGs were selected to construct prognostic risk score signatures. Immunohistochemistry was utilized to manifest the differential expression of six FRGs in tumor and normal tissues at the protein level. Functional enrichment analysis indicated that FRGs were mainly enriched in ferroptosis-related pathways. Patients were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier survival curves confirmed that patients with a high score had significantly worse overall survival. Receiver operating characteristic (ROC) curves proved that the prognostic signature has good sensitivity and specificity for predicting the prognosis of LUAD patients. Nomogram analysis showed that the prognostic signature has potential independent prognostic value. Moreover, the prognostic signature has been shown to be significantly associated with some clinical features (T stage, N stage, tumor stage, and survival status) as well as many immune-activity-related genes and immune-checkpoint-related genes. In conclusion, we constructed a prognostic signature consisting of six FGRs, which can provide a reference for predicting the prognosis of LUAD patients.

Zhou J ，Wang X ，Li Z ，Jiang R ... -  《FEBS Open Bio》

Risk stratification of lung adenocarcinoma using a nomogram combined with ferroptosis-related LncRNAs and subgroup analysis with immune and N6-methyladenosine modification.

Determining the prognosis of lung adenocarcinoma (LUAD) is challenging. The present study aimed to identify prognostic ferroptosis-related long noncoding RNAs (FRLs) and construct a prognostic model. Moreover, differential analysis of immune and N6-methyladenosine (m6A)-related genes was systematically conducted. A total of 504 patients selected from a dataset from The Cancer Genome Atlas were included. The patients with LUAD were randomly divided into a training group and a test group at a ratio of 1:1. Pearson correlation analysis and univariate Cox regression analysis were used to identify the prognostic FRLs. Then, a prognostic model was constructed from the optimized subset of prognostic FRLs based on the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, the receiver operating characteristic (ROC) curve and survival analysis were used to evaluate the performance of the model. The risk score based on the prognostic model was analyzed using Cox regression analysis. Moreover, gene set enrichment analysis and differential analysis of immune- and m6A-related genes were conducted. After univariate Cox regression analysis and LASSO algorithm analysis, a total of 19 prognostic FRLs were selected to construct the final model to obtain the risk score. The area under the ROC curve of the prognostic model for 1-year, 3-year, and 5-year overall survival (OS) was 0.763, 0.745, and 0.778 in the training set and 0.716, 0.724, and 0.736 in the validation set, respectively. Moreover, the OS of the high-risk group was significantly worse than that of the low-risk group in the training group (P < 0.001) and in the test group (P < 0.001). After univariate and multivariate Cox regression analysis, the risk score [hazard ratio (HR) = 1.734; P < 0.001] and stage (HR = 1.557; P < 0.001) were both considered significant prognostic factors for LUAD. A nomogram was constructed based on clinical features and risk score. The expression of 34 checkpoint genes and 13 m6A-related genes varied significantly between the two risk groups. This study constructed a prognostic model to effectively predict the OS of patients with LUAD, and these OS-related FRLs might serve as potential therapeutic targets of LUAD.

Gao C ，Kong N ，Zhang F ，Tang T ，Li J ，Ding H ，Sun Z ，Wu L ，Xu M ... -  《BMC Medical Genomics》