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Background:  Increasing evidence has demonstrated that immune-related long non-coding RNAs (irlncRNAs) are critically involved in tumor initiation and progression and associated with the prognosis of various cancers. However, their role in soft tissue sarcoma (STS) remains significantly uninvestigated.   Materials and Methods:  Gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the identification of irlncRNAs. Univariate analysis and modified least absolute shrinkage and selection operator (LASSO) penalized regression analysis were employed to determine differently expressed irlncRNA (DEirlncRNA) pairs of prognostic value, and subsequently, a risk signature based on DEirlncRNA pairs was established. Furthermore, Kaplan–Meier analysis and the area under the receiver operating characteristic curve (AUC) were used to assess survival differences and the predictive accuracy of the risk signature, respectively. Lastly, the correlation of irlncRNAs with immune characteristics and chemosensitivity in patients with STS were further investigated.   Results:  A total of 1088 irlncRNAs were identified, and 311 irlncRNAs were distinguished as DEirlncRNAs. A total of 130 DEirlncRNA pairs were further identified as prognostic markers, and 14 pairs were selected for establishing a risk signature. The irlncRNA-based risk signature functioned as an independent prognostic marker for STS. Compared with the patients in the high-risk group, those in the low-risk group exhibited a better prognosis and were more sensitive to several chemotherapeutic agents. In addition, the irlncRNA-based risk signature was significantly associated with immune scores, infiltrating immune cells, and the expression of several immune checkpoints.   Conclusion:  In conclusion, our data revealed that the irlncRNA-based risk signature resulted in reliable prognosis, effectively predicted the immune landscape of patients with STS and was significantly correlated with chemosensitivity, thus providing insights into the potential role of irlncRNAs as prognostic biomarkers and novel therapeutic targets for STS.

frontiers in cell and developmental biology

Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma