Abstract
Background: N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) are critically involved in cancer development. However, the roles and clinical significance of m6A-related lncRNAs in soft tissue sarcomas (STS) are inconclusive, thereby warranting further investigations. Methods: Transcriptome profiling data were extracted from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). Consensus clustering was employed to divide patients into clusters and Kaplan–Meier analysis was used to explore the prognostic differences between the subgroups. Gene set enrichment analysis (GSEA) was conducted to identify the biological processes and signaling pathways associated with m6A-Related lncRNAs. Finally, patients were randomly divided into training and validation cohorts, and least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to establish the m6A-related lncRNA-based risk signature. Results: A total of 259 STS patients from TCGA-SARC dataset were enrolled in our study. Thirteen m6A-Related lncRNAs were identified to be closely related to the prognosis of STS patients. Patients were divided into two clusters, and patients in cluster 2 had a better overall survival (OS) than those in cluster 1. Patients in different clusters also showed differences in immune scores, infiltrating immune cells, and immune checkpoint expression. Patients were further classified into high-risk and low-risk subgroups according to risk scores, and high-risk patients were found to have a worse prognosis. The receiver operating characteristic (ROC) curve indicated that the risk signature displayed excellent performance at predicting the prognosis of patients with STS. Further, the risk signature was remarkably connected with the immune microenvironment and chemosensitivity in STS. Conclusion: Our study demonstrated that m6A-related lncRNAs were significantly associated with prognosis and tumor immune microenvironment and could function as independent prognosis-specific predictors in STS, thereby providing novel insights into the roles of m6A-related lncRNAs in STS.
Highlights
Soft tissue sarcomas (STS) are a heterogeneous group of various rare tumors of mesenchymal origin that most frequently occur in the extremities (Bourcier et al, 2019)
Our study demonstrated that m6A-related lncRNAs were significantly associated with prognosis and tumor immune microenvironment and could function as
The results revealed that the expression level of seven prognostic m6A-related lncRNAs was markedly higher whereas that of six prognostic m6A-related lncRNAs was significantly lower in normal samples than in STS tumor samples (p < 0.001) (Figures 2C,D)
Summary
Soft tissue sarcomas (STS) are a heterogeneous group of various rare tumors of mesenchymal origin that most frequently occur in the extremities (Bourcier et al, 2019). Despite recent progress in STS treatment, including surgery, chemotherapy, and radiotherapy, the survival rates of patients with advanced STS still need to be improved. The 5-year survival rate of advanced STS patients is as low as 27.2% (Kim et al, 2019). Approximately 50% of STS patients would eventually develop distant metastases, which remains as a major cause of death and poses an obstacle to effective treatment (Italiano et al, 2011). It is difficult to predict the prognosis of patients with STS (Jo and Fletcher, 2014). There is an urgent need to identify novel biomarkers to predict prognosis and evaluate the risks for STS patients. The roles and clinical significance of m6A-related lncRNAs in soft tissue sarcomas (STS) are inconclusive, thereby warranting further investigations
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