The Study of Sarcoma Microenvironment Heterogeneity Associated With Prognosis Based on an Immunogenomic Landscape Analysis

摘要

Microenvironment-driven tumor heterogeneity causes the limitation of immunotherapy of sarcomas. Nonetheless, systematical studies of various molecular levels can enhance the understanding of tumor microenvironment (TME) related to prognosis and provide novel insights of precision immunotherapy. Three prognostic-related TME phenotypes were identified by consensus clustering of the relative infiltration of 22 immune cells from 869 samples of sarcomas. Additionally, integrative immunogenomic analysis is applied to explore the characteristics of different TME groups. The results revealed that most of the immune cell infiltration is higher in the better prognostic group, which are more affected by lower DNA methylation levels and fewer copy number variations in the worse prognostic group. The signaling pathway crosstalk analysis suggested that the changes in the tumor microenvironment will cause considerable variation in the flow of information between pathways, especially when the degree of relative infiltration of immune cells is low, patient's endocrine system may also be significantly affected. Also, the endogenous competitive network analysis indicated that several differentially expressed long non-coding RNAs (lncRNAs) associated with the prognosis or tumor recurrence of sarcoma patients affected the regulatory relationship between miRNAs and different genes when the sarcoma microenvironment changes. In summary, the significant relationship between genetic alterations and prognostic-related TME characteristics in sarcomas were determined in this study. These findings may provide new clues for the treatment of sarcomas.