研究概要
这一发现揭示了 PRCC 中两个独立的预后相关 DEFAGs,并建立了一个稳健的预后模型,为该疾病的治疗提供了潜在的治疗靶点和有前景的见解。
研究思路结论见上方概要
背景
本研究旨在识别乳头状肾细胞癌(PRCC)中与预后相关的差异表达铁死亡相关基因(DEFAGs)。
方法
PRCC 患者的简单核苷酸变异、转录组谱及相关临床信息数据来源于 The Cancer Genome Atlas (TCGA) 数据库。使用 R 中的“limma”包分析铁死亡相关基因 (FAGs) 的表达矩阵,以识别差异表达的 DEFAGs。采用 Lasso 回归分析,以及单因素和多因素 Cox 比例风险回归,识别独立的预后相关 DEFAGs 并制定列线图。此外,我们检查了潜在的独立生存相关临床风险因素,并比较了高风险和低风险患者组之间的免疫细胞浸润和肿瘤突变负荷 (TMB) 差异。
结果
对321例患者队列进行分析,发现12个FAGs显著影响PRCC患者的总体生存期(OS)。其中,两个mRNA(GCLC、HSBP1)成为独立的预后相关DEFAGs。吸烟状况、肿瘤分期和风险评分被确定为PRCC的独立临床危险因素。此外,在高危组和低危组之间观察到免疫细胞浸润和功能的显著差异。GCLC和HSBP1与多种免疫细胞和功能、TMB以及免疫逃逸相关。
展开英文摘要原文
BACKGROUND
This study aimed to identify the prognostic-related differentially expressed ferroptosis-associated genes (DEFAGs) in papillary renal cell carcinoma (PRCC).
METHODS
Data encompassing simple nucleotide variation, transcriptome profiles, and relevant clinical information of PRCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The expression matrix of ferroptosis-associated genes (FAGs) was analyzed using the "limma" package in R to identify differentially expressed DEFAGs. Lasso regression analysis, along with univariate and multivariate Cox proportional hazards regressions, was employed to identify independent prognostic-related DEFAGs and formulate a nomogram. Additionally, we examined potential independent survival-related clinical risk factors and compared immune cell infiltration and tumor mutation burden (TMB) differences between high- and low-risk patient groups.
RESULTS
A cohort of 321 patients were analyzed, revealing twelve FAGs significantly influencing the overall survival (OS) of PRCC patients. Among them, two mRNAs (GCLC, HSBP1) emerged as independent prognostic-related DEFAGs. Smoking status, tumor stage, and risk score were identified as independent clinical risk factors for PRCC. Furthermore, notable disparities in immune cell infiltration and function were observed between high- and low-risk groups. GCLC and HSBP1 were associated with various immune cells and functions, TMB, and immune evasion.
CONCLUSION
This finding revealed two independent prognostic-related DEFAGs in PRCC and established a robust prognostic model, offering potential therapeutic targets and promising insights for the management of this disease.
论文信息
- 作者
- Chen YB、Yang X、Lv D、Tang LY、Liu YW
- 第一作者单位
- Department of Urology, People's Hospital of Deyang City, 173#Northern Taishan Road, Deyang, 618000, China.China
- 通讯作者单位
- Department of Laboratory, People's Hospital of Deyang City, 173#Northern Taishan Road, Deyang, 618000, China. ywliu_mail@126.com.China
- 期刊
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2025 Mar