AUTHOR=Wang Xinwen , Wang Liangming , Xu Weifeng , Wang Xinwu , Ke Dianshan , Lin Jinluan , Lin Wanzun , Bai Xiaochun 

TITLE=Classification of Osteosarcoma Based on Immunogenomic Profiling

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.696878

DOI=10.3389/fcell.2021.696878

ISSN=2296-634X

ABSTRACT=Accumulating evidence has supported that osteosarcoma is heterogeneous, and several subtypes have been identified based on the genomic profiling. Immunotherapy is revolutionizing cancer treatment and is a promising therapeutic strategy. Whereas, few studies have identified osteosarcoma classification based on immune biosignatures, which offer the optimal stratification of individuals befitting immunotherapy. Here, we classified osteosarcoma into two clusters: immunity high and immunity low using the single-sample gene-set enrichment analysis (ssGSEA) and unsupervised hierarchical clustering. Immunity_H subtype was associated with high immune cells infiltration, a favorable prognosis, benefit to immunotherapy, high HLA genes expression, and activated immune signal pathway indicating an immune-hot phenotype. On the contrary, Immunity_L subtype was correlated with low immune cells infiltration, poor prognosis, and cancer-related pathway indicating an immune-cold phenotype. We also identified TYROBP as a key immunoregulatory gene that associated with CD8+ T cell infiltration by multiplex immunohistochemistry (mIHC). Finally, we established an immune-related prognostic model that predicted the survival time of osteosarcoma. In conclusion, we established a new classification system of osteosarcoma based on immune signatures and identified TYROBP as a key immunoregulatory gene. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of osteosarcoma patients.