由铁死亡相关基因(FAG)构建的乳头状肾细胞癌(PRCC)预后模型及其与肿瘤突变负荷(TMB)和免疫浸润的关系。
A prognostic model constructed by ferroptosis-associated genes (FAGs) in papillary renal cell carcinoma (PRCC) and its association with tumor mutation burden (TMB) and immune infiltration.
发表日期:2024 Aug 16
作者:
Yong-Bo Chen, Xin Yang, Dong Lv, Liang-You Tang, Ying-Wen Liu
来源:
Cellular & Molecular Immunology
摘要:
本研究旨在鉴定乳头状肾细胞癌(PRCC)中与预后相关的差异表达铁死亡相关基因(DEFAG)。PRCC患者的简单核苷酸变异、转录组谱和相关临床信息的数据来源于癌症基因组图谱(TCGA)数据库。使用 R 中的“limma”包分析铁死亡相关基因 (FAG) 的表达矩阵,以识别差异表达的 DEFAG。采用 Lasso 回归分析以及单变量和多变量 Cox 比例风险回归来识别独立的预后相关 DEFAG 并制定列线图。此外,我们还检查了潜在的独立生存相关临床危险因素,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。对 321 名患者的队列进行了分析,揭示了 12 个 FAG 显着影响总体风险PRCC 患者的生存期 (OS)。其中,两个 mRNA(GCLC、HSBP1)作为独立的预后相关 DEFAG 出现。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,在高风险组和低风险组之间观察到免疫细胞浸润和功能的显着差异。 GCLC和HSBP1与各种免疫细胞和功能、TMB和免疫逃避相关。这一发现揭示了PRCC中两个独立的与预后相关的DEFAG,并建立了稳健的预后模型,为该疾病的管理提供了潜在的治疗靶点和有希望的见解。 © 2024。作者。
This study aimed to identify the prognostic-related differentially expressed ferroptosis-associated genes (DEFAGs) in papillary renal cell carcinoma (PRCC).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.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.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.© 2024. The Author(s).