New gene signature from the dominant infiltration immune cell type in osteosarcoma predicts overall survival

Abstract

The immune microenvironment of osteosarcoma (OS) has been reported to play an important role in disease progression and prognosis. However, owing to tumor heterogeneity, it is not ideal to predict OS prognosis by examining only infiltrating immune cells. This work aimed to build a prognostic gene signature based on similarities in the immune microenvironments of OS patients. Public datasets were used to examine the correlated genes, and the most consistent dominant infiltrating immune cell type was identified. The LASSO Cox regression model was used to establish a multiple-gene risk prediction signature. A nine-gene prognostic signature was generated from the correlated genes for M0 macrophages and then proven to be effective and reliable in validation cohorts. Signature comparison indicated the priority of the signature. Multivariate Cox regression models indicated that the signature risk score is an independent prognostic factor for OS patients regardless of the Huvos grade in all datasets. In addition, the results of the association between the signature risk score and chemotherapy sensitivity also showed that there was no significant difference in the sensitivity of any drugs between the low- and high-risk groups. A GSEA of GO and KEGG pathways found that antigen processing- and presentation-related biological functions and olfactory transduction receptor signaling pathways have important roles in signature functioning. Our findings showed that M0 macrophages were the dominant infiltrating immune cell type in OS and that the new gene signature is a promising prognostic model for OS patients.

Exploring osteosarcoma based on the tumour microenvironment

“…In contrast, high expression of PPARG was positively associated with the low-risk score group, which played the role of oncogene, which was consistent with the ndings of previous scholars mentioned above, and further proved the accuracy of the risk model.While the high expression of PDK1 is proportional to the high expression of Macrophages M0 and inversely proportional to the high expression of Macrophages M2, the opposite is true in PPARG. Combined with previous studies by scholars, Shao et al demonstrated that Macrophages M2 has a pro-carcinogenic role in osteosarcoma [30], and the role of Macrophages M0 for osteosarcoma is still unclear [31], therefore, immunotherapy targeting Macrophages M0 and Macrophages M2 may become a promising therapeutic strategy for the treatment of osteosarcoma.…”