Lin Zhengjun, Xu Yiting, Zhang Xianghong, Wan Jia, Zheng Tao, Chen Hongxuan, Chen Shijie, Liu Tang
Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.
Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, People's Republic of China.
Int J Gen Med. 2021 Nov 16;14:8263-8279. doi: 10.2147/IJGM.S335073. eCollection 2021.
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.
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.
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.
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.
细胞焦亡与癌症的发生和发展密切相关，多种长链非编码RNA（lncRNA）可对其进行调控。然而，细胞焦亡相关lncRNA在软组织肉瘤（STS）中的作用仍 largely未知。
我们的研究共纳入了从癌症基因组图谱肉瘤（TCGA-SARC）数据集中提取的259例STS患者。从癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）下载每百万映射读数中每千碱基转录本的基因表达数据片段每百万映射读数（FPKM）值，以研究细胞焦亡相关lncRNA的表达模式。基于细胞焦亡相关lncRNA进行无监督聚类，并研究细胞焦亡相关lncRNA与临床结局和免疫微环境的关联。构建了总生存（OS）和无病生存（DFS）的两个风险特征，并在独立队列中进行验证。
在STS中总共鉴定出166种细胞焦亡相关lncRNA。通过无监督聚类将患者分为两个亚组，第2组预后较好，免疫评分较高，免疫细胞丰度较高，一些免疫检查点的表达较高。分别基于10种和13种细胞焦亡相关lncRNA构建并验证了具有良好区分度的OS和DFS风险特征。高风险患者预后良好，受试者工作特征（ROC）曲线表明这两个风险特征均可作为STS患者预后的优秀预测指标。此外，OS风险特征还可以出色地预测STS的免疫格局。
总之，我们的研究揭示了细胞焦亡相关lncRNA在STS中的临床意义和关键作用，并构建了基于细胞焦亡相关lncRNA的新型风险特征，可有效预测STS的临床结局和免疫微环境。
