Identification and Validation of Pyroptosis-Related lncRNA Signature and Its Correlation with Immune Landscape in Soft Tissue Sarcomas

Zhengjun Lin,1,2 Yiting Xu,2 Xianghong Zhang,1 Jia Wan,1 Tao Zheng,1 Hongxuan Chen,1 Shijie Chen,3 Tang Liu1 1Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People’s Republic of China; 3Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, People’s Republic of ChinaCorrespondence: Shijie ChenDepartment of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, 410006, Hunan, People’s Republic of ChinaTel +86-73185292111Email shijiechencsu@163.comTang LiuDepartment of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaTel +86-73185292111Email liutang1204@csu.edu.cnBackground: Pyroptosis is critically associated with cancer initiation and progression, which can be modulated by diverse long noncoding RNAs (lncRNAs). However, the roles of pyroptosis-related lncRNAs in soft tissue sarcomas (STS) are still largely unknown.Methods: Our study included a total of 259 STS patients extracted from The Cancer Genome Atlas Sarcoma (TCGA-SARC) dataset. Gene expression data fragments per kilobase of transcript per million mapped reads (FPKM) values were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the investigation of the expression pattern of pyroptosis-related lncRNAs. Unsupervised clustering based on pyroptosis-related lncRNAs was performed, and the associations of pyroptosis-related lncRNAs with clinical outcomes and immune microenvironment were investigated. Two risk signatures for overall survival (OS) and disease-free survival (DFS) were constructed and validated in independent cohorts.Results: A total of 166 pyroptosis-related lncRNAs were identified in STS. Patients were clustered into two subgroups by unsupervised clustering, and cluster 2 had better prognoses, higher immune scores, higher abundance of immune cells, and higher expression of some immune checkpoints. OS- and DFS-risk signatures based on 10 and 13 pyroptosis-related lncRNAs, respectively, with favorable discrimination were constructed and validated. High-risk patients had favorable prognoses, and receiver operating characteristic (ROC) curves showed that both risk signatures could function as excellent predictors for prognoses of STS patients. Besides, the OS-risk signature could also excellently predict the immune landscape of STS.Conclusion: In conclusion, our study revealed the clinical significance and critical roles of pyroptosis-related lncRNAs in STS, and constructed novel risk signatures based on pyroptosis-related lncRNAs that could effectively predict clinical outcomes and immune microenvironment in STS.Keywords: pyroptosis, immune microenvironment, prognostic signature, soft tissue sarcomas