Investigating the prognostic value of constructing disulfidptosis-related gene models for lung adenocarcinoma patients

- OBJECTIVE: Disulfidptosis is a novel mode of cell death, a programmed mode of intracellular disulfide accumulation due to solute carrier family 7 member 11 (SLC7A11)-mediated abnormalities in the cell membrane cystine trans-port system. Numerous studies have confirmed the prominent role played by SLC7A11 in tumors, but the involvement of SLC7A11 as an important mediator of disulfidptosis in the death process of lung adenocarcinoma cells remains unclear. MATERIALS AND METHODS: We obtained 4,107 SLC7A11-related genes and analyzed them using a total of 1,040 lung adenocarcinoma tran-scriptome sequencing data from The Cancer Genome Atlas (TCGA) cohort and GEO (Gene Expression Omnibus) cohort and 991 relevant clinical data. First, we screened for differential genes and identified molecular subtypes for as-sessing characteristic differences between lung adenocarcinoma subtypes under the influence of SLC7A11-associated genes. Then, risk score models were constructed to assess the prog-nosis, immune infiltration, tumor microenviron-ment, and drug treatment effects in lung ade-nocarcinoma patients. Finally, we also analyzed the distribution of cell types and expression of characteristic genes within the tumor using a single-cell database. In addition, relevant drug sensitivities were predicted. RESULTS: We screened 956 genes with signif-icant differences and identified 2 molecular sub-types and found significant differences in their prognosis and that subtype B had a significantly better survival prognosis than subtype A. In ad-dition, we found that pathways associated with cell proliferation division and DNA repair were enriched in the high-risk type A samples. Final-ly, we constructed a robust risk-scoring system, and our risk analysis revealed a general reduc-tion of various immune cell components and tu-mor stromal components in the immune micro -environment of high-risk lung adenocarcinoma and a distinct immune infiltration pattern of im-mune cells, which was associated with a lower survival rate.CONCLUSIONS: Our comprehensive analy-sis of SLC7A11-related genes suggests that di-sulfidptosis has a potential value in the tumor microenvironment, immunity, clinical outcome, and prognosis of lung adenocarcinoma. These findings may increase our understanding of di-sulfidptosis as a novel cell death paradigm and provide ideas for assessing the prognosis of lung adenocarcinoma and developing new diag-nostic and therapeutic strategies.