Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.
Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.
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DOI：
10.1038/s41467-022-34689-5
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发表时间：
2022-11-23
影响因子：
16.6
通讯作者：
Hua, Yingqi
中科院分区：
文献类型：
--
作者：
Jiang, Yafei;Wang, Jinzeng;Sun, Mengxiong;Zuo, Dongqing;Wang, Hongsheng;Shen, Jiakang;Jiang, Wenyan;Mu, Haoran;Ma, Xiaojun;Yin, Fei;Lin, Jun;Wang, Chongren;Yu, Shuting;Jiang, Lu;Lv, Gang;Liu, Feng;Xue, Linghang;Tian, Kai;Wang, Gangyang;Zhou, Zifei;Lv, Yu;Wang, Zhuoying;Zhang, Tao;Xu, Jing;Yang, Liu;Zhao, Kewen;Sun, Wei;Tang, Yujie;Cai, Zhengdong;Wang, Shengyue;Hua, Yingqi
骨肉瘤（OS）是一种原发性恶性骨肿瘤，最常见于儿童、青少年和年轻人。在这里，我们全面分析了121例OS患者的基因组，表观基因组和转录组数据。体细胞突变在群组内是多样的，并且仅TP 53显著突变。通过多组学数据的无监督综合聚类，我们将OS分为四种具有不同分子特征和临床预后的亚型：（1）免疫激活（S-IA），（2）免疫抑制（S-IS），（3）同源重组缺陷显性（S-HRD），和（4）MYC驱动（S-MD）。具有HR熟练性肿瘤的MYC扩增被鉴定为具有高氧化磷酸化特征，导致对新辅助化疗的抗性。为每种亚型确定了潜在的治疗靶点，包括基于铂的化疗、免疫检查点抑制剂、抗VEGFR、抗MYC和基于PARPi的合成致死策略。我们全面的综合表征提供了一个有价值的资源，加深了我们对疾病的理解，并可能指导未来的临床策略，为精确治疗骨肉瘤的生存率已在很大程度上保持不变，几十年来，治疗反应是可变的。在这里，作者分析了121例骨肉瘤患者的基因组、转录组和表观基因组数据，并确定了与治疗结果相关的亚型。
Osteosarcoma (OS) is a primary malignant bone tumor that most commonly affects children, adolescents, and young adults. Here, we comprehensively analyze genomic, epigenomic and transcriptomic data from 121 OS patients. Somatic mutations are diverse within the cohort, and only TP53 is significantly mutated. Through unsupervised integrative clustering of the multi-omics data, we classify OS into four subtypes with distinct molecular features and clinical prognosis: (1) Immune activated (S-IA), (2) Immune suppressed (S-IS), (3) Homologous recombination deficiency dominant (S-HRD), and (4) MYC driven (S-MD). MYC amplification with HR proficiency tumors is identified with a high oxidative phosphorylation signature resulting in resistance to neoadjuvant chemotherapy. Potential therapeutic targets are identified for each subtype, including platinum-based chemotherapy, immune checkpoint inhibitors, anti-VEGFR, anti-MYC and PARPi-based synthetic lethal strategies. Our comprehensive integrated characterization provides a valuable resource that deepens our understanding of the disease, and may guide future clinical strategies for the precision treatment of OS. Osteosarcoma survival rates have been largely unchanged for several decades, and treatment response is variable. Here, the authors analyzed genomic, transcriptomic and epigenomic data from 121 osteosarcoma patients and identify subtypes related to treatment outcome.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium