Characterization of ROS Metabolic Equilibrium Reclassifies Pan-Cancer Samples and Guides Pathway Targeting Therapy.
Characterization of ROS Metabolic Equilibrium Reclassifies Pan-Cancer Samples and Guides Pathway Targeting Therapy.
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ROS 代谢平衡的表征重新分类泛癌症样本并指导靶向治疗
DOI：
10.3389/fonc.2020.581197
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发表时间：
2020
影响因子：
4.7
通讯作者：
Wu A
中科院分区：
文献类型：
--
作者：
Shen S;Yan Z;Wu J;Liu X;Guan G;Zou C;Guo Q;Zhu C;Liu T;Chen C;Chen L;Cheng P;Cheng W;Wu A
背景：氧化还原平衡异常是肿瘤恶性和耐药的主要因素。了解活性氧（ROS）代谢是阐明肿瘤氧化还原状态的关键。然而，我们评估肿瘤组织中ROS的方法有限，对人类癌症中ROS代谢的了解也很少。方法：对22种癌症类型的癌症基因组图谱多组学数据和癌症药物敏感性基因组学数据进行分析。通过细胞活力测试和异种移植模型验证ROS调节在调节治疗效果中的作用。结果：建立并验证了反映ROS代谢平衡五个维度的ROS指标。基于ROS指标，我们绘制了22种癌症类型的ROS代谢景观，发现ROS代谢在不同癌症类型中发挥着不同的作用。肿瘤样本被分为8个ROS簇，它们具有不同的临床和多组学特征，而这些特征与它们的组织学来源无关。我们建立了基于ROS的药物疗效评价网络，并通过实验验证了预测的效果，提示调节ROS代谢可提高治疗敏感性，扩大药物应用范围。结论：本研究提出了一种新的评估ROS状态的方法，对人类癌症中ROS代谢平衡有了全面的认识，对临床管理具有实际意义。
Background: Abnormal redox equilibrium is a major contributor to tumor malignancy and treatment resistance. Understanding reactive oxygen species (ROS) metabolism is a key to clarify the tumor redox status. However, we have limited methods to evaluate ROS in tumor tissues and little knowledge on ROS metabolism across human cancers. Methods: The Cancer Genome Atlas multi-omics data across 22 cancer types and the Genomics of Drug Sensitivity in Cancer data were analyzed in this study. Cell viability testing and xenograft model were used to validate the role of ROS modulation in regulating treatment efficacy. Results: ROS indexes reflecting ROS metabolic balance in five dimensions were developed and verified. Based on the ROS indexes, we conducted ROS metabolic landscape across 22 cancer types and found that ROS metabolism played various roles in different cancer types. Tumor samples were classified into eight ROS clusters with distinct clinical and multi-omics features, which was independent of their histological origin. We established a ROS-based drug efficacy evaluation network and experimentally validated the predicted effects, suggesting that modulating ROS metabolism improves treatment sensitivity and expands drug application scopes. Conclusion: Our study proposes a new method in evaluating ROS status and offers comprehensive understanding on ROS metabolic equilibrium in human cancers, which provide practical implications for clinical management.
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癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
9.3
作者：
Ryu, Ka-Young;Lee, Hyun-Ju;Hoe, Hyang-Sook
通讯作者：
Hoe, Hyang-Sook
影响因子：
11.5
作者：
Laurent, Anouchka P.;Siret, Aurelie;Malinge, Sebastien
通讯作者：
Malinge, Sebastien
影响因子：
11.5
作者：
Felsberg, Joerg;Hentschel, Bettina;Weller, Michael
通讯作者：
Weller, Michael