A Novel Pyroptosis-Related Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Osteosarcoma.

ABSTRACT

Osteosarcoma is a common malignant bone tumor with a propensity for drug resistance, recurrence, and metastasis. A growing number of studies have elucidated the dual role of pyroptosis in the development of cancer, which is a gasdermin-regulated novel inflammatory programmed cell death. However, the interaction between pyroptosis and the overall survival (OS) of osteosarcoma patients is poorly understood. This study aimed to construct a prognostic model based on pyroptosis-related genes to provide new insights into the prognosis of osteosarcoma patients. We identified 46 differentially expressed pyroptosis-associated genes between osteosarcoma tissues and normal control tissues. A total of six risk genes affecting the prognosis of osteosarcoma patients were screened to form a pyroptosis-related signature by univariate and LASSO regression analysis and verified using GSE21257 as a validation cohort. Combined with other clinical characteristics, including age, gender, and metastatic status, we found that the pyroptosis-related signature score, which we named "PRS-score," was an independent prognostic factor for patients with osteosarcoma and that a low PRS-score indicated better OS and a lower risk of metastasis. The result of ssGSEA and ESTIMATE algorithms showed that a lower PRS-score indicated higher immune scores, higher levels of tumor infiltration by immune cells, more active immune function, and lower tumor purity. In summary, we developed and validated a pyroptosis-related signature for predicting the prognosis of osteosarcoma, which may contribute to early diagnosis and immunotherapy of osteosarcoma.