Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer.
Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer.
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免疫相关风险特征的鉴定与免疫表型相关并预测尿路上皮癌的抗 PD-L1 疗效
DOI：
10.3389/fcell.2021.646982
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发表时间：
2021
影响因子：
5.5
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Li P;Hao S;Ye Y;Wei J;Tang Y;Tan L;Liao Z;Zhang M;Li J;Gui C;Xiao J;Huang Y;Chen X;Cao J;Luo J;Chen W
免疫检查点抑制(ICI)治疗已被用于治疗晚期尿路上皮癌。分子标志物可能会改善尿路上皮癌患者的危险分层和ICI益处的预测。我们从肿瘤基因组图谱(TCGA)数据集中分析了406例膀胱尿路上皮癌，鉴定出161个信使RNA(MRNAs)是差异表达的免疫基因(DEIGs)。利用套索Cox回归模型，建立了基于8个m RNA的风险特征。我们在348例转移性尿路上皮癌(MUC)样本中验证了这种免疫相关风险信号的预后和预测准确性，这些样本接受了IMLIGN210的抗PD-L1(阿特唑珠单抗)治疗。我们构建了基于ANXA1、IL22、IL9R、KLRK1、LRP1、NRG3、SEMA6D和STAP2这8个mRNAs的免疫相关风险特征。基于八个信使核糖核酸的风险签名成功地将患者分为高风险组和低风险组。无论是初始TCGA训练组、内部TCGA测试组、所有TCGA组还是ICI治疗组，这些组之间的总体存活率都有显著差异。高危人群与低危人群的危险比(HR)分别为3.65(p<；0.0001)、2.56(p<；0.0001)、3.36(p<；0.0001)和2.42(p=0.0009)。风险标志是预测生存的独立预后因素。此外，风险特征与免疫特性有关。在不同的肿瘤突变负荷(TMB)亚组中，它成功地将患者分为高危和低危两组，临床结果差异显著。我们的基于八个信使核糖核酸的风险标记是尿路上皮癌的一个稳定的生物标记物，并且可能能够预测哪些患者从ICI治疗中受益。它可能在精确的个体化免疫治疗中发挥作用。
Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p < 0.0001), 2.56 (p < 0.0001), 3.36 (p < 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.
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影响因子：
2
作者：
Ternes, Nils;Rotolo, Federico;Michiels, Stefan
通讯作者：
Michiels, Stefan
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T
影响因子：
3.7
作者：
Gonias SL;Karimi-Mostowfi N;Murray SS;Mantuano E;Gilder AS
通讯作者：
Gilder AS
影响因子：
28.4
作者：
Li, Bailiang;Cui, Yi;Li, Ruijiang
通讯作者：
Li, Ruijiang