Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment

Yafei Jiang, Jinzeng Wang, Mengxiong Sun, Dongqing Zuo, Hongsheng Wang, Jiakang Shen, Wenyan Jiang, Haoran Mu, Xiaojun Ma, Fei Yin, Jun Lin, Chongren Wang, Shuting Yu, Lu Jiang, Gang Lv, Feng Liu, Linghang Xue, Kai Tian, Gangyang Wang, Zifei Zhou, Yu Lv, Zhuoying Wang, Tao Zhang, Jing Xu, Liu Yang, Kewen Zhao, Wei Sun, Yujie Tang, Zhengdong Cai (), Shengyue Wang () and Yingqi Hua ()
Additional contact information
Yafei Jiang: Shanghai Jiao Tong University School of Medicine
Jinzeng Wang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Mengxiong Sun: Shanghai Jiao Tong University School of Medicine
Dongqing Zuo: Shanghai Jiao Tong University School of Medicine
Hongsheng Wang: Shanghai Jiao Tong University School of Medicine
Jiakang Shen: Shanghai Jiao Tong University School of Medicine
Wenyan Jiang: Shanghai Jiao Tong University School of Medicine
Haoran Mu: Shanghai Jiao Tong University School of Medicine
Xiaojun Ma: Shanghai Jiao Tong University School of Medicine
Fei Yin: Shanghai Jiao Tong University School of Medicine
Jun Lin: Shanghai Jiao Tong University School of Medicine
Chongren Wang: Shanghai Jiao Tong University School of Medicine
Shuting Yu: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Lu Jiang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Gang Lv: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Feng Liu: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Linghang Xue: Shanghai Jiao Tong University School of Medicine
Kai Tian: Shanghai Jiao Tong University School of Medicine
Gangyang Wang: Shanghai Jiao Tong University School of Medicine
Zifei Zhou: Shanghai Jiao Tong University School of Medicine
Yu Lv: Shanghai Jiao Tong University School of Medicine
Zhuoying Wang: Shanghai Jiao Tong University School of Medicine
Tao Zhang: Shanghai Jiao Tong University School of Medicine
Jing Xu: Shanghai Jiao Tong University School of Medicine
Liu Yang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Kewen Zhao: Shanghai Jiao Tong University School of Medicine
Wei Sun: Shanghai Jiao Tong University School of Medicine
Yujie Tang: Shanghai Jiao Tong University School of Medicine
Zhengdong Cai: Shanghai Jiao Tong University School of Medicine
Shengyue Wang: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yingqi Hua: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34689-5

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