Prognostic Implications of Novel Ten-Gene Signature in Uveal Melanoma.
Prognostic Implications of Novel Ten-Gene Signature in Uveal Melanoma.
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葡萄膜黑色素瘤中新的十基因特征的预后意义
DOI：
10.3389/fonc.2020.567512
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发表时间：
2020
影响因子：
4.7
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
Luo H;Ma C;Shao J;Cao J
背景：葡萄膜黑色素瘤（UM）是成人最常见的原发性眼内肿瘤。基因组研究提供了深入了解分子亚组和致癌驱动程序的UM，可能会导致新的治疗策略。研究方法：从TCGA门户下载的数据集TCGA-UVM被设置为训练队列，从GEO数据库获得的数据集GSE 22138被设置为验证队列。训练队列采用Kaplan-Meier分析和单因素考克斯回归模型初步筛选预后相关基因。此外，采用LASSO的考克斯回归模型构建多基因签名，然后通过Kaplan-Meier、考克斯和ROC分析在验证队列中验证。此外，通过斯皮尔曼检验评估拷贝数畸变与风险评分之间的相关性。进行GSEA和免疫浸润分析以理解功能注释和标记在肿瘤微环境中的作用。结果如下：构建了十个基因签名，并通过Kaplan-Meier分析进行检查，发现总生存期、无进展生存期和无转移生存期存在显着差异。通过考克斯回归分析，进一步证明与其他临床病理参数相比，十基因签名是独立的风险因素。此外，受试者工作特征曲线（ROC）分析结果表明，我们的签名具有更好的UM预后预测能力。10个基因签名与染色体3、8 q、6 q和6p的拷贝数显著相关。此外，GSEA和免疫浸润分析表明，签名与免疫相关途径和肿瘤环境有密切的相互作用。结论：鉴定10个基因标签（SIRT 3、HMCES、SLC 44 A3、TCTN 1、STPG 1、POMGNT 2、RNF 208、ANXA 2 P2、ULBP 1和CA 12）可以准确地识别患者的预后，并且与免疫显性肿瘤环境密切相关，这可能为UM患者提供个性化的预后预测和新的治疗见解。
Background: Uveal melanoma (UM) is the most common primary intraocular cancer in adults. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of UM that may lead to novel therapeutic strategies. Methods: Dataset TCGA-UVM, download from TCGA portal, were taken as the training cohort, and dataset GSE22138, obtained from GEO database, was set as the validation cohort. In training cohort, Kaplan–Meier analysis and univariate Cox regression model were applied to preliminary screen prognostic genes. Besides, the Cox regression model with LASSO was implemented to build a multi-gene signature, which was then validated in the validation cohorts through Kaplan–Meier, Cox, and ROC analyses. In addition, the correlation between copy number aberrations and risk score was evaluated by Spearman test. GSEA and immune infiltrating analyses were conducted for understanding function annotation and the role of the signature in the tumor microenvironment. Results: A ten-gene signature was built, and it was examined by Kaplan–Meier analysis revealing that significantly overall survival, progression-free survival, and metastasis-free survival difference was seen. The ten-gene signature was further proven to be an independent risk factor compared to other clinic-pathological parameters via the Cox regression analysis. Moreover, the receiver operating characteristic curve (ROC) analysis results demonstrated a better predictive power of the UM prognosis that our signature owned. The ten-gene signature was significantly correlated with copy numbers of chromosome 3, 8q, 6q, and 6p. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and the tumor environment. Conclusions: Identifying the ten-gene signature (SIRT3, HMCES, SLC44A3, TCTN1, STPG1, POMGNT2, RNF208, ANXA2P2, ULBP1, and CA12) could accurately identify patients' prognosis and had close interactions with the immunodominant tumor environment, which may provide UM patients with personalized prognosis prediction and new treatment insights.
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DOI：
10.12659/msm.899595
发表时间：
2017-01-26
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Dai X;Dong M;Yu H;Xie Y;Yu Y;Cao Y;Kong Z;Zhou B;Xu Y;Yang T;Li K
通讯作者：
Li K
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
DOI：
10.1097/iop.0000000000000833
发表时间：
2017-09-01
影响因子：
2
作者：
Glass, Lora R. Dagi;Lawrence, Donald P.;Freitag, Suzanne K.
通讯作者：
Freitag, Suzanne K.
影响因子：
4.5
作者：
Lee, Nayoung;Zakka, Labib R.;Schatton, Tobias
通讯作者：
Schatton, Tobias
影响因子：
16.6
作者：
Durante, Michael A.;Rodriguez, Daniel A.;Harbour, J. William
通讯作者：
Harbour, J. William