FDX1参与了铜依赖性细胞死亡的一种方式——杯形细胞死亡，这可能会影响类似于铁死和火死的肿瘤进程。然而，FDX1在肿瘤中的作用尚待探索。本研究从全癌症的角度基于综合生物信息学，调查了FDX1的表达特征、与预后、肿瘤分期、免疫微环境以及杯形细胞死亡的相关性。FDX1 mRNA和临床数据从癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和Broad Institute癌症细胞线百科全书(CCLE)数据库获得。在GEPIA2.0上执行了肿瘤分期的FDX1差异表达。使用Cox比例风险回归和生存曲线分析FDX1的预后价值。探讨FDX1表达与免疫浸润、免疫细胞、免疫检查点、肿瘤突变负荷(TMB)、微卫星不稳定(MSI)、错配修复(MMR)和DNA甲基转移酶(DNMT)的关系。 GSEA被用来发现FDX1在LGG中的生物学功能。结果显示，FDX1在多种肿瘤类型中异常表达，并在不同的肿瘤分期中表现出变异性。生存分析显示，FDX1预测GBMLGG、LGG中不良预后，而在KIPAN和KIRC中预示着良好预后。免疫相关分析表明，在LGG中，FDX1与基质得分(StromalScore)、免疫得分(ImmuneScore)、ESTIMATEScore呈正相关，而在KIRC中呈负相关。此外，在全癌症分析中，FDX1与免疫细胞浸润、免疫检查点、肿瘤干细胞、同源重组缺陷(HRD)和TMB呈正相关。在LGG中，通过CGGA的验证表明FDX1具有预后价值和免疫相关性。具体来说，高FDX1表达伴随着CD276(B7-H3)、CD274(PD-L1)、PDCD1LG2(PD-L2)、CTLA4和HAVCR2等免疫检查点的高表达。这些发现说明FDX1可能被视为LGG中的潜在不良预后生物标志物和免疫治疗预测因子。Copyright © 2023 Huang, Wu, Zhu, Luo, Wang, Liu and Cheng.

FDX1 participates in cuproptosis, a copper-dependent cell death mode, which might influence tumor progressions like ferroptosis and pyroptosis. However, the role of FDX1 in tumors remains to be explored. This study investigated FDX1 expression features, and correlations to prognosis, tumor stages, immune microenvironment, and cuproptosis from a pan-cancer perspective based on integrated bioinformatics. FDX1 mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Broad Institute Cancer Cell Line Encyclopedia (CCLE) databases. Differential expression of FDX1 in tumor stages was performed on GEPIA2.0. Cox proportional hazard regression and survival curve were used to analyze the prognostic value of FDX1. The relationships between FDX1 expression and immune infiltration, immune cells, immune checkpoints, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) were explored. GSEA was utilized to find the biological function of FDX1 in LGG. Results showed that FDX1 was abnormally expressed in multiple tumor types and demonstrated variability in various tumor stages. Survival analysis revealed FDX1 predicted poor prognosis in glioma (GBMLGG), brain lower-grade glioma (LGG), and good prognosis in the pan-kidney cohort (KIPAN), and kidney renal clear cell carcinoma (KIRC). Immune correlation analysis suggested FDX1 showed positive correlations to StromalScore, ImmuneScore, ESTIMATEScore in LGG and negative correlation in KIRC. Additionally, positive correlations were observed between FDX1 and immune cells infiltration, immune checkpoints, tumor stemness, homologous recombination deficiency (HRD), and TMB in LGG in the pan-cancer analysis. Validation with CGGA suggested prognostic value and immune correlation of FDX1 in LGG. Specifically, high expression of FDX1 was accompanied by high expression of immune checkpoints such as CD276 (B7-H3), CD274 (PD-L1), PDCD1LG2 (PD-L2), CTLA4, and HAVCR2. These findings illustrated that FDX1 might be considered a potential poor prognosis biomarker and immunotherapy predictor in LGG.Copyright © 2023 Huang, Wu, Zhu, Luo, Wang, Liu and Cheng.