The Potential of Five Immune-Related Prognostic Genes to Predict Survival and Response to Immune Checkpoint Inhibitors for Soft Tissue Sarcomas Based on Multi-Omic Study

作者：Hui-Yun Gu, Lulu Lin, Chao Zhang, Min Yang, Hou-Cheng Zhong, Renxiong Wei · 发表于：Frontiers in Oncology · 年份：2020 · DOI：10.3389/fonc.2020.01317 · 被引用次数：24 · 研究领域：Cancer Immunotherapy and Biomarkers、Sarcoma Diagnosis and Treatment、Lymphoma Diagnosis and Treatment

Low response rates to immunotherapy have been reported in soft tissue sarcoma (STS). There are few predictive biomarkers of response, and the tumor immune microenvironment associated with progression and prognosis remains unclear in STS. Gene expression data from the Cancer Genome Atlas were used to identify the immune-related prognostic genes (IRPGs) and construct the immune gene-related prognostic model (IGRPM). The tumor immune microenvironment was characterized to reveal differences between patients with different prognoses. Furthermore, somatic mutation data and DNA methylation data were analyzed to understand the underlying mechanism leading to different prognoses. The IGRPM was constructed using five IRPGs (IFIH1, CTSG, STC2, SECTM1, and BIRC5). Two groups (high- and low-risk patients) were identified based on the risk score. Low-risk patients with higher overall survival time had higher immune scores, more immune cell infiltration (e.g., CD8 T cell and activated natural killer cells), higher expression of immune-stimulating molecules, higher stimulating cytokines and corresponding receptors, higher innate immunity molecules, and stronger antigen-presenting capacity. However, inhibition of immunity was observed in low-risk patients owing to the higher expression of immune checkpoint molecules and inhibiting cytokines. High-risk patients had high tumor mutation burden, which did not significantly influence survival. Gene set enrichment analysis further revealed that pat...