Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma.
Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma.
复制标题
葡萄膜黑色素瘤铁死亡介导的修饰模式和肿瘤免疫微环境特征分析
DOI：
10.3389/fcell.2021.685120
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Cao K
中科院分区：
文献类型：
--
作者：
Jin Y;Wang Z;He D;Zhu Y;Gong L;Xiao M;Chen X;Cao K
葡萄膜黑色素瘤（UVM）是成人眼内恶性肿瘤，其中约50%的患者发展为转移性疾病并且具有不良预后。对免疫疗法的需求迅速出现，最近的研究取得了令人印象深刻的结果。新出现的证据表明，铁凋亡是一种新型的细胞死亡，可能介导肿瘤浸润免疫细胞影响抗癌免疫。在本研究中，我们首先通过考克斯分析从训练集（TCGA和GSE 84976数据库）中选择UVM样本中的11个铁凋亡调节剂。然后我们根据STRING数据库将这些分子分为模块A和B，并使用一致性聚类分析对两个模块中的基因进行分类。根据基因本体论（GO）、京都基因和基因组百科全书（KEGG）和基因集富集分析（GSEA），结果显示模块A中的簇与免疫相关通路显著相关。接下来，我们应用了ESTIMATE和CIBERSORT算法，发现这些铁凋亡相关模式可能会影响一定比例的TME浸润细胞，从而介导肿瘤免疫环境。此外，为了进一步开发基于免疫景观的预后特征，我们在训练集中建立了一个六基因调节剂预后模型，并在验证集中成功验证了它（GSE 44295和GSE 27831）。随后，我们确定了关键分子，包括ABCC1，CHAC1和GSS，它们与总生存率，无进展生存率，疾病特异性生存率和无进展间隔相关。我们构建了一个竞争性的内源性RNA网络，包括29个lncRNA，12个miRNAs和25个铁凋亡相关的mRNA，以进一步阐明机制。我们的研究结果表明，铁凋亡相关基因可能是合适的潜在生物标志物，为UVM预后提供新的见解，并破译肿瘤微环境特征的潜在机制。
Uveal melanoma (UVM) is an intraocular malignancy in adults in which approximately 50% of patients develop metastatic disease and have a poor prognosis. The need for immunotherapies has rapidly emerged, and recent research has yielded impressive results. Emerging evidence has implicated ferroptosis as a novel type of cell death that may mediate tumor-infiltrating immune cells to influence anticancer immunity. In this study, we first selected 11 ferroptosis regulators in UVM samples from the training set (TCGA and GSE84976 databases) by Cox analysis. We then divided these molecules into modules A and B based on the STRING database and used consensus clustering analysis to classify genes in both modules. According to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the results revealed that the clusters in module A were remarkably related to immune-related pathways. Next, we applied the ESTIMATE and CIBERSORT algorithms and found that these ferroptosis-related patterns may affect a proportion of TME infiltrating cells, thereby mediating the tumor immune environment. Additionally, to further develop the prognostic signatures based on the immune landscape, we established a six-gene-regulator prognostic model in the training set and successfully verified it in the validation set (GSE44295 and GSE27831). Subsequently, we identified the key molecules, including ABCC1, CHAC1, and GSS, which were associated with poor overall survival, progression-free survival, disease-specific survival, and progression-free interval. We constructed a competing endogenous RNA network to further elucidate the mechanisms, which consisted of 29 lncRNAs, 12 miRNAs, and 25 ferroptosis-related mRNAs. Our findings indicate that the ferroptosis-related genes may be suitable potential biomarkers to provide novel insights into UVM prognosis and decipher the underlying mechanisms in tumor microenvironment characterization.
登录
查看更多内容
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
DOI：
10.1007/bf00186516
发表时间：
1996-01-01
影响因子：
2.7
作者：
deWaardSiebinga, I;Hilders, CGJM;Jager, MJ
通讯作者：
Jager, MJ
影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.
影响因子：
3.6
作者：
Achberger S;Aldrich W;Tubbs R;Crabb JW;Singh AD;Triozzi PL
通讯作者：
Triozzi PL