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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 , 2022. "Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34689-5
    DOI: 10.1038/s41467-022-34689-5
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