A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.
A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.
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DOI：
10.3390/diagnostics11020219
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发表时间：
2021-02-02
期刊：
影响因子：
--
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Luo H;Ma C
背景：葡萄膜黑色素瘤（UM）是成人最常见的眼内肿瘤。铁凋亡是一种新认识的细胞死亡过程，在形态学、生物化学和遗传学上与其他形式的细胞死亡不同，在肿瘤生物学中起着至关重要的作用。本研究的目的是构建一个具有UM预后能力的铁中毒相关基因的基因签名。研究方法：将来自癌症基因组图谱（TCGA）的UM患者作为训练组群，并且将来自基因表达综合（GEO）的GSE 22138作为验证组群。从基因卡中共检索到103个铁中毒相关基因。我们进行了Kaplan-Meier和单变量考克斯分析，以初步筛选训练队列中具有潜在预后能力的铁中毒相关基因。然后将这些基因应用于基于总体生存率的LASSO考克斯回归模型，构建基因签名。然后通过Kaplan-Meier（KM）、考克斯和ROC分析在两个组群中评估发现的基因签名。Pearson相关系数检验了风险评分与UM常见突变和自噬之间的相关性。进行GSEA和免疫浸润的分析以更好地研究基因签名的功能注释和肿瘤微环境中各种免疫细胞的特征。结果如下：从训练队列中发现了一个七基因标签，并通过Kaplan-Meier和考克斯回归分析在所有队列中进行了验证，揭示了其在UM中的独立预后价值。此外，进行了ROC分析，证实了该特征对UM预后的强预测能力。共发现52.24%（256/490）的自噬相关基因与危险度评分显著相关。对GSEA和免疫浸润的详细分析显示了与七基因签名相关的特定途径，也证实了肥大细胞静息在七基因签名的预后中发挥的关键作用。结论：在这项研究中，建立了一个新的铁蛋白沉积相关的七个基因标签（ALOX 12，CD 44，MAP 1 LC 3C，STEAP 3，HMOX 1，ITGA 6和AIFM 2/FSP 1）。它可以准确地预测UM预后，并与肥大细胞静息相关，这为UM人群的个性化结局预测和新疗法的开发提供了可能。
Background: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM. Methods: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan–Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan–Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment. Results: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan–Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature. Conclusions: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.
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影响因子：
15.9
作者：
Balint, K;Xiao, M;Liu, ZJ
通讯作者：
Liu, ZJ
DOI：
10.1016/j.bbrc.2020.01.066
发表时间：
2020-03-19
影响因子：
3.1
作者：
Dai, Enyong;Zhang, Wenlong;Tang, Daolin
通讯作者：
Tang, Daolin
影响因子：
14.2
作者：
Dudeck, Anne;Koeberle, Martin;Biedermann, Tilo
通讯作者：
Biedermann, Tilo
影响因子：
64.8
作者：
Hangauer MJ;Viswanathan VS;Ryan MJ;Bole D;Eaton JK;Matov A;Galeas J;Dhruv HD;Berens ME;Schreiber SL;McCormick F;McManus MT
通讯作者：
McManus MT
DOI：
10.1152/ajprenal.00044.2017
发表时间：
2018-05-01
影响因子：
4.2
作者：
Adedoyin, Oreoluwa;Boddu, Ravindra;Agarwal, Anupam
通讯作者：
Agarwal, Anupam