Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma.
Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma.
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弥漫性大 B 细胞淋巴瘤的免疫表型景观和预后相关 mRNA 特征
DOI：
10.3389/fgene.2022.872001
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
弥漫性大B细胞淋巴瘤（DLBCL）表现出高度复杂的免疫系统。在这项研究中，我们打算确定不同的免疫表型，并检查免疫相关的mRNA签名的临床特征，治疗反应性以及危险分层和生存预测DLBCL。我们根据28种免疫细胞类型鉴定了DLBCL患者的两种免疫浸润亚型。GSEA分析揭示了DLBCL的两种稳健显著亚型的一致分类。考虑到免疫浸润亚型用于预后预测的方便应用，我们基于免疫-H和免疫-L组之间的差异表达基因开发了风险评分。采用LASSO-考克斯回归模型，建立了一个包含ANTXR 1、CD 3D、TIMP 1、FPR 3、NID 2、CTLA 4、LPAR 6、GPR 183、LYZ、PTGDS、ITK、FBN 1、FRMD 6、PLAU、MICAL 2、C1 S等16个基因的风险特征。综合结果显示，高危组与较低的免疫浸润、较强的侵袭性表型、较低的总生存率和对来那度胺更敏感相关。相比之下，低风险组评分与较高的免疫浸润、较低的侵袭性表型、较好的总生存期以及更有可能从PD-1/PD-L1抑制剂中获益相关。最后，验证了由风险评分和IPI评分组成的诺模图比传统的临床预测模型更准确地预测DLBCL的总生存期。总而言之，我们的数据证明了DLBCL内免疫模式的异质性，并加深了我们对这种肿瘤实体的分子理解。
Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We identified two immune infiltration subtypes of DLBCL patients based on 28 immune cell types. GSEA analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Considering the convenient application of the immune infiltration subtypes for prognostic prediction, we developed a risk score based on the differentially expressed genes between the Immunity-H and Immunity-L groups. By a least absolute shrinkage and selection operator (LASSO)-Cox regression model, a sixteen-gene risk signature, comprising ANTXR1, CD3D, TIMP1, FPR3, NID2, CTLA4, LPAR6, GPR183, LYZ, PTGDS, ITK, FBN1, FRMD6, PLAU, MICAL2, C1S, was established. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.
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DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
影响因子：
45.3
作者：
Bartlett, Nancy L.;Wilson, Wyndham H.;Leonard, John P.
通讯作者：
Leonard, John P.
影响因子：
4.6
作者：
Sheikh, Semira;Kuruvilla, John
通讯作者：
Kuruvilla, John
影响因子：
6.5
作者：
Feldman T;Mato AR;Chow KF;Protomastro EA;Yannotti KM;Bhattacharyya P;Yang X;Donato ML;Rowley SD;Carini C;Valentinetti M;Smith J;Gadaleta G;Bejot C;Stives S;Timberg M;Kdiry S;Pecora AL;Beaven AW;Goy A
通讯作者：
Goy A
DOI：
10.1093/annonc/mdy450
发表时间：
2018-12-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Ciavarella S;Vegliante MC;Fabbri M;De Summa S;Melle F;Motta G;De Iuliis V;Opinto G;Enjuanes A;Rega S;Gulino A;Agostinelli C;Scattone A;Tommasi S;Mangia A;Mele F;Simone G;Zito AF;Ingravallo G;Vitolo U;Chiappella A;Tarella C;Gianni AM;Rambaldi A;Zinzani PL;Casadei B;Derenzini E;Loseto G;Pileri A;Tabanelli V;Fiori S;Rivas-Delgado A;López-Guillermo A;Venesio T;Sapino A;Campo E;Tripodo C;Guarini A;Pileri SA
通讯作者：
Pileri SA