4.7 Article

The hypoxia-related signature predicts prognosis, pyroptosis and drug sensitivity of osteosarcoma

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.814722

Keywords

hypoxia; osteosarcoma; pyroptosis; drug resistance; prognosis

Funding

  1. Fundamental Research Funds for the Central Universities of Central South University [2020zzts896]
  2. Qinghai Key Laboratory of Laboratory Medicine [105]
  3. guiding project of Qinghai Provincial Health and Family Planning Commission [2018-wjzdx17]
  4. Project of Kunlun Elite, High-End Innovation and Entrepreneurship Talents of Qinghai Province (2021) [13]
  5. National Natural Science Foundation of China [82260365]

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This study investigates the relationship between hypoxia, pyroptosis, tumor immune microenvironment, chemosensitivity, and prognosis in osteosarcoma. The findings suggest that hypoxia can influence the tumor immune microenvironment and promote pyroptosis, leading to poor prognosis and low chemosensitivity. The study also develops hypoxia and pyroptosis risk models based on gene data and clinical data, which can predict the prognosis and chemotherapy sensitivities of osteosarcoma patients.
Osteosarcoma (OS) is one of the most common types of solid sarcoma with a poor prognosis. Solid tumors are often exposed to hypoxic conditions, while hypoxia is regarded as a driving force in tumor recurrence, metastasis, progression, low chemosensitivity and poor prognosis. Pytoptosis is a gasdermin-mediated inflammatory cell death that plays an essential role in host defense against tumorigenesis. However, few studies have reported relationships among hypoxia, pyroptosis, tumor immune microenvironment, chemosensitivity, and prognosis in OS. In this study, gene and clinical data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases were merged to develop a hypoxia risk model comprising four genes (PDK1, LOX, DCN, and HMOX1). The high hypoxia risk group had a poor prognosis and immunosuppressive status. Meanwhile, the infiltration of CD8(+) T cells, activated memory CD4(+) T cells, and related chemokines and genes were associated with clinical survival outcomes or chemosensitivity, the possible crucial driving forces of the OS hypoxia immune microenvironment that affect the development of pyroptosis. We established a pyroptosis risk model based on 14 pyroptosis-related genes to independently predict not only the prognosis but also the chemotherapy sensitivities. By exploring the various connections between the hypoxic immune microenvironment and pyroptosis, this study indicates that hypoxia could influence tumor immune microenvironment (TIM) remodeling and promote pyroptosis leading to poor prognosis and low chemosensitivity.

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