AUTHOR=Zhang Anran , Yang Jinpo , Ma Chao , Li Feng , Luo Huan 

TITLE=Development and Validation of a Robust Ferroptosis-Related Prognostic Signature in Lung Adenocarcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.616271

DOI=10.3389/fcell.2021.616271

ISSN=2296-634X

ABSTRACT=Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in morphology, biochemistry and genetics, and has played a vital role in cancer biology. This study aimed to identify a ferroptosis-related gene signature associated with LUAD prognosis.
Methods: Dataset TCGA-LUAD came from TCGA portal, was taken as training cohort. GSE72094 and GSE68465 from GEO database, was treated as validation cohorts. 259 ferroptosis-related genes were retrieved from the FerrDb database. In the training cohort, Kaplan-Meier and univariate Cox analysis were conducted for preliminary screening of ferroptosis-related genes with potential prognostic capacity. These genes then entered into the LASSO Cox regression model, constructing a gene signature. The latter was then evaluated in the training and validation cohorts via Kaplan-Meier, Cox, and ROC analyses. In addition, the correlations between risk score and autophagy were examined by Pearson correlation coefficient. The analyses of GSEA and immune infiltrating were performed for better studying the function annotation of the gene signature and the character of each kind of immune cells played in the tumor microenvironment.
Results: A fifteen-gene signature was found from the training cohort and validated by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in LUAD. Moreover, the ROC analysis conducted confirming a strong predictive ability that this signature owned for LUAD prognosis. 151/222 (68.01%) autophagy-related genes were discovered significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited the specific pathways that associate with the fifteen-gene signature and identified the crucial roles of Mast cells resting and Dendritic cells resting owned in the prognosis of the fifteen-gene signature.
Conclusions: In this present study, a novel ferroptosis-related fifteen-gene signature (RELA, ACSL3, YWHAE, EIF2S1, CISD1, DDIT4, RRM2, PANX1, TLR4, ARNTL, LPIN1, HERPUD1, NCOA4, PEBP1, and GLS2) was built. It could accurately predict the prognosis of LUAD and was related to Mast cells resting and Dendritic cells resting, which provide potential for the personalized outcome prediction and the development of new therapies in LUAD population.