Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.
Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.
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基因组分析揭示了铁死亡对于透明细胞肾细胞癌的预后和免疫原性特征。
DOI：
10.1016/j.omtn.2021.05.009
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发表时间：
2021-09-03
期刊：
影响因子：
--
通讯作者：
Sugiyama H
中科院分区：
文献类型：
--
作者：
Bai D;Feng H;Yang J;Yin A;Lin X;Qian A;Sugiyama H
在这项研究中，通过铁死亡与肿瘤微环境（TME）之间的相互作用，系统地研究了透明细胞肾细胞癌（ccRCC）中铁死亡的特征模式。基于57个铁死亡相关基因（FRGs）的mRNA表达谱，构建了三种铁死亡模式，它们具有不同的预后和免疫细胞浸润情况（特别是T细胞和树突状细胞）。高铁死亡评分的特征是预后较差、T细胞浸润增加、免疫和基质评分较高、肿瘤突变负荷升高以及对抗CTLA4免疫治疗的反应增强。同时，低铁死亡评分与肿瘤纯度提高以及氨基酸和脂肪酸代谢途径显著相关。经过验证，铁死亡评分是一个独立且有效的预后因素。总之，铁死亡可能参与多样且复杂的肿瘤微环境。对铁死亡模式的评估可能会加深对肿瘤微环境中免疫浸润的理解，帮助肿瘤学家制定个体化的免疫治疗策略。
系统地研究了透明细胞肾细胞癌（ccRCC）中铁死亡的特征。与T细胞浸润增加、免疫和基质评分较高、肿瘤突变负荷升高以及抗CTLA4反应增强相关的铁死亡评分参与肿瘤微环境，因此可能影响抗PD - 1治疗中的免疫治疗队列（GEO：GSE78220和IMvigor210）。
In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis patterns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prognosis, increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced response to anti-CTLA4 immunotherapy. Meanwhile, the low ferroptosis scores were distinctly associated with enhanced tumor purity and amino acid and fatty acid metabolism pathways. Following validation, the ferroptosis score was an independent and effective prognostic factor. Collectively, ferroptosis could be involved in the diverse and complex TME. Evaluation of the ferroptosis patterns may heighten the comprehension about immune infiltrations in the TME, assisting oncologists to generate individualized immunotherapeutic strategies. Characteristics of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated. Ferroptosis scores associated with increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced anti-CTLA4 response involved in tumor microenvironment therefore are likely to affect the immunotherapy cohorts (GEO: GSE78220 and IMvigor210) in anti-PD-1 treatment.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
10.1
作者：
McKay RR;Bossé D;Xie W;Wankowicz SAM;Flaifel A;Brandao R;Lalani AA;Martini DJ;Wei XX;Braun DA;Van Allen E;Castellano D;De Velasco G;Wells JC;Heng DY;Fay AP;Schutz FA;Hsu J;Pal SK;Lee JL;Hsieh JJ;Harshman LC;Signoretti S;Motzer RJ;Feldman D;Choueiri TK
通讯作者：
Choueiri TK
影响因子：
254.7
作者：
Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
64.5
作者：
Hugo W;Zaretsky JM;Sun L;Song C;Moreno BH;Hu-Lieskovan S;Berent-Maoz B;Pang J;Chmielowski B;Cherry G;Seja E;Lomeli S;Kong X;Kelley MC;Sosman JA;Johnson DB;Ribas A;Lo RS
通讯作者：
Lo RS
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