Inflammasome‐related gene signatures as prognostic biomarkers in osteosarcoma

Author:

Zhang Nan1,Han Ying23,Cao Hangkai4,Wang Qingxin4ORCID

Affiliation:

1. Department of Medical Oncology China Coast Guard Hospital of the People's Armed Police Force Zhejiang China

2. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine Zhejiang China

3. Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Zhejiang China

4. Department of Orthopaedic Surgery China Coast Guard Hospital of the People's Armed Police Zhejiang China

Abstract

AbstractOsteosarcoma, the primary bone cancer in adolescents and young adults, is notorious for its aggressive growth and metastatic potential. Our study delved into the prognostic impact of inflammasome‐related gene signatures in osteosarcoma patients, employing comprehensive genetic profiling to uncover signatures linked with patient outcomes. We identified three patient subgroups through consensus clustering, with one showing worse survival rates correlated with high FGFR3 and RARB expressions. Immune profiling revealed significant immune cell infiltration differences among these subgroups, affecting survival. Utilising advanced machine learning, including StepCox and gradient boosting machine algorithms, we developed a prognostic model with a notable c‐index of 0.706, highlighting CD36 and MYD88 as key genes. Higher inflammasome risk scores from our model were associated with poorer survival, corroborated across datasets. In vitro experiments validated CD36 and MYD88's roles in promoting osteosarcoma cell proliferation, invasion and migration, emphasising their therapeutic potential. This research offers new insights into inflammasomes' role in osteosarcoma, introducing novel biomarkers for risk assessment and potential therapeutic targets. Our findings suggest a pathway towards personalised treatment strategies, potentially improving patient outcomes in osteosarcoma.

Funder

Science and Technology Bureau of Jiaxing City

Publisher

Wiley

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