m(6)A modification patterns and tumor immune landscape in clear cell renal carcinoma.
m(6)A modification patterns and tumor immune landscape in clear cell renal carcinoma.
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透明细胞肾癌中的 m6A 修饰模式和肿瘤免疫格局
DOI：
10.1136/jitc-2020-001646
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发表时间：
2021-03
影响因子：
10.9
通讯作者：
Zeng G
中科院分区：
文献类型：
--
作者：
Zhong J;Liu Z;Cai C;Duan X;Deng T;Zeng G
最近的研究集中在N6-甲基腺苷（m6 A）修饰和特异性肿瘤浸润免疫细胞之间的相关性。然而，m6 A修饰在肿瘤免疫格局中的潜在作用仍然难以捉摸。我们综合评估了513例肾透明细胞癌（ccRCC）患者的m6 A修饰模式和肿瘤免疫景观，并将m6 A修饰模式与免疫景观相关联。采用主成分分析法建立m6 Ascore。进行多变量考克斯回归分析以评估m6 Ascore的预后价值。我们确定了三个m6 Aclusters的特点是在Th 17签名，肿瘤内异质性，整体细胞增殖，非整倍体，免疫调节基因的表达，整体体细胞拷贝数的变化，和预后的差异。建立m6 Ascore以量化个体ccRCC患者的m6 A修饰模式。进一步分析显示m6 Ascore是ccRCC的独立预后因素。最后，我们验证了m6 Ascore在晚期ccRCC患者的程序性细胞死亡蛋白1（PD-1）阻断治疗中的预后价值。该研究证明了m6 A修饰与ccRCC中的肿瘤免疫景观之间的相关性。在个体ccRCC患者中对m6 A修饰模式的综合评估增强了我们对肿瘤免疫格局的理解，并为ccRCC患者提供了新的和改进的免疫策略的新方法。
Recent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive. We comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore. We identified three m6Aclusters—characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC. This study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.
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影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
168.9
作者：
Rini, Brian I.;Powles, Thomas;Motzer, Robert J.
通讯作者：
Motzer, Robert J.
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
DOI：
10.1126/science.aaf1490
发表时间：
2016-03-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGranahan N;Furness AJ;Rosenthal R;Ramskov S;Lyngaa R;Saini SK;Jamal-Hanjani M;Wilson GA;Birkbak NJ;Hiley CT;Watkins TB;Shafi S;Murugaesu N;Mitter R;Akarca AU;Linares J;Marafioti T;Henry JY;Van Allen EM;Miao D;Schilling B;Schadendorf D;Garraway LA;Makarov V;Rizvi NA;Snyder A;Hellmann MD;Merghoub T;Wolchok JD;Shukla SA;Wu CJ;Peggs KS;Chan TA;Hadrup SR;Quezada SA;Swanton C
通讯作者：
Swanton C
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