Cuproptosis, a new type of programmed cell death, is involved in the development and progression of malignancies. The study of cuproptosis-associated long non-coding RNAs (lncRNAs) in soft tissue sarcomas (STSs) is however limited. There is also uncertainty regarding the prognostic accuracy of cuproptosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. The aim of this study was to determine the prognostic significance of cuprotosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. Transcriptomic and clinical data from patients with STSs were obtained through The Cancer Genome Atlas (TCGA). Overall, 259 patients were randomly allocated to a training group or a testing group. In the training group, a cuproptosis-associated lncRNA signature was constructed, and the signature was verified in the testing group. On the basis of risk scores and clinical features, we later developed a hybrid nomogram. We also performed functional and tumor immune microenvironment analysis based on the cuproptosis-associated lncRNA signature. A signature of 5 cuproptosis-associated lncRNAs was created. Based on this signature, we categorized STS patients into high-risk and low-risk groups. The study showed that patients at high risk had a worse prognosis than those at low risk. A nomogram was then constructed combining clinical characteristics with the risk scores, and it was shown to have credible predictive power. Functional enrichment and tumor immune microenvironmental analyses showed that high-risk STSs tend to be immunologically sensitive tumors. In our study, we found a cuproptosis-associated lncRNAs signature, which serves as an independent prognostic indicator. Cuproptosis-associated lncRNAs may play a role in the tumor immune microenvironment, which might be a therapeutic target for patients with STSs.

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