背景:膀胱癌(BLCA)是一种影响泌尿系统的常见恶性肿瘤,在全球范围内对发病率和死亡率都造成了巨大负担。在所有BLCA案件中,非肌层浸润性膀胱癌约占总数的75%.近年来,铁性死亡的概念,以脂质过氧化物的积累为标志的铁依赖性调节细胞死亡形式,引起了全世界研究人员的注意。然而,铁凋亡相关基因(FRGs)在抗BLCA反应中的确切参与仍未得到充分阐明。
方法:来自TCGA和GEO数据集的BLCA样本的整合促进了FRGs的定量评估,提供对其预测能力的潜在见解。利用包含mRNAsi的丰富信息,基因突变,CNV,TMB,这些数据集中的临床特征进一步丰富了分析,增强其鲁棒性和可靠性。通过利用Lasso回归,建立了预测模型,能够在BLCA的背景下进行准确的预后评估。此外,共表达分析揭示了基因表达模式与FRGs之间的复杂关系,揭示它们在BLCA中的功能相关性和潜在意义。
结果:FRGs在BLCA患者高危队列中表达水平升高,即使没有其他临床指标,表明它们作为预后标志物的潜力。GSEA揭示了免疫和肿瘤相关途径的富集,特别是在高危人群中。此外,低危组和高危组之间的免疫功能和m6a基因表达存在显著差异.几个基因,包括MYBPH,SOST,SPRR2A,和CRNN,被发现可能参与BLCA的致癌过程。此外,CYP4F8、PDZD3、CRTAC1和LRTM1被鉴定为潜在的抑癌基因。两个风险组之间的免疫功能和m6a基因表达存在显着差异,进一步强调了与不同预后结果相关的独特分子特征。值得注意的是,在预后模型之间观察到了很强的相关性,CNVs,SNPs,和药物敏感性。
结论:FRGs与BLCA的发病和进展有关。FRGs签名为预测BLCA提供了一个可行的替代方案,这些FRGs显示了未来BLCA靶向治疗的前瞻性研究领域。
BACKGROUND: Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and poses a significant burden in terms of both incidence and mortality rates on a global scale. Among all BLCA cases, non-muscle invasive bladder cancer constitutes approximately 75% of the total. In recent years, the concept of ferroptosis, an iron-dependent form of regulated cell death marked by the accumulation of lipid peroxides, has captured the attention of researchers worldwide. Nevertheless, the precise involvement of ferroptosis-related genes (FRGs) in the anti-BLCA response remains inadequately elucidated.
METHODS: The integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of FRGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and FRGs, unraveling their functional relevance and potential implications in BLCA.
RESULTS: FRGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including MYBPH, SOST, SPRR2A, and CRNN, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CYP4F8, PDZD3, CRTAC1, and LRTM1 were identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles.
CONCLUSIONS: FRGs are associated with the onset and progression of BLCA. A FRGs signature offers a viable alternative to predict BLCA, and these FRGs show a prospective research area for BLCA targeted treatment in the future.