Comprehensive analyses of Disulfidptosis-related genes on prognosis and immune infiltration in lung adenocarcinoma
Authors: Xiong Renhui , Wang Jiaxin , Han Xiangjie , Yang Shuoqi , Luo Zhong , Yan Yunbo , Li Yaping , Cao Chang’an , Chen Xiaodong , Chen Zhaohong , Lian Wenqin , Jia Chiyu , Zhang Zexin , Yin Bin 
Published: August 2023

Abstract
Conclusion: The current study revealed the prognostic and immunogenetic values of DRGs, especially SLC7A11 and SLC3A2, which might be potential prognostic biomarkers and targets for immunotherapy of LUAD.
Background: Lung adenocarcinoma (LUAD) has the highest incidence in lung cancers, which ranks first in incidence and mortality among various cancers. Programmed cell death is crucial to the development of cancers. Disulfidptosis is a novel type of cell death associated with SLC7A11high expression and glucose starvation, however, the role of disulfidptosis related genes (DRGs) in LUAD remains unclear.
Methods: Transcriptomic data of LUAD and healthy samples were downloaded from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue (GTEx) database to describe the expression of DRGs. RT-qPCR was used to evaluate the expression of DRGs in four LUAD cell lines. The protein expression patterns were obtained from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the human protein atlas (HPA) database. Furthermore, clinical relevance of DRGs in LUAD were assessed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Prognosis and cox regression analyses were carried out to explore the prognostic value of DRGs. Meanwhile, Genetic mutations were evaluated by cBioPortal database. Additionally, the immune subtype characterization, stromal scores, immune scores, and ESTIMATE scores of DRGs were valued. Next, correlation analysis between key DRGs and immune infiltration was performed by CIBERSORT and TIMER 2.0 database. Finally, the potential function and interacting molecule of DRGs were further analyzed by GO and KEGG.
Results: The most of DRGs were up-regulated in tumor tissues and showed a relatively high mutation frequency. DRGs were positively associated with hazard ratio with Overall Survival (OS) especially SLC3A2. Survival and univariate cox regression analysis revealed that SLC3A2 and SLC7A11 were significantly associated with poor prognosis in LUAD patients. Furthermore, both SLC3A2 and SLC7A11 were negatively correlated with the estimate score and immune scores. SLC3A2 had the highest expression in C1 immune subtype and the lowest in C3 subtype, while SLC7A11 highest in C1 immune subtype and lowest in C4 subtype. In addition, SLC3A2 and SLC7A11 were related to CD4+ cells, CD8+ cells, B cells, Macrophage M0, Mast cell resting, and Eosinophil in pan-cancer analysis. Besides, SLC3A2 was correlated with immuno-stimulator (CD276, TNDSF9, TNFRSF14 and TNFSF13) and immuno-inhibitor (TGFB1, PVRL2, ADORA2A, LGALS9 and TGFBR1) while SLC7A11 was link to immune-stimulator (CD48, ULBP1, TNFRSF25, CD48 and CD40LG) and immuno-inhibitor (PVRL2, KD, CD160 and CD96). The results suggested that SLC7A11 and SLC3A2 were distinctly correlated with higher immune infiltration. Finally, KEGG and GO analysis results indicated DRGs contributed to metabolism, oxidative respiratory cycle chain especially tricarboxylic acid cycle in LUAD.