Table3_Identification and Validation of a Novel Pyroptosis-Related Gene Signature for Prognosis Prediction in Soft Tissue Sarcoma.DOCX

Soft tissue sarcoma (STS) represents an uncommon and heterogenous group of malignancies, and poses substantial therapeutic challenges. Pyroptosis has been demonstrated to be related with tumor progression and prognosis. Nevertheless, no studies exist that delineated the role of pyroptosis-related genes (PRGs) in STS. In the present study, we comprehensively and systematically analyzed the gene expression profiles of PRGs in STS. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were utilized to identify differentially expressed PRGs. In total, 34 PRGs were aberrantly expressed between STS and normal tissues. Several PRGs were validated with RT-qPCR. Consensus clustering analysis based on PRGs was conducted to divide STS patients into two clusters, and significant survival difference was observed between two distinct clusters (p = 0.019). Differentially expressed genes (DEGs) were identified between pyroptosis-related clusters. Based on the least absolute shrinkage and selection operator (LASSO) COX regression analysis, the pyroptosis-related gene signature with five key DEGs was constructed. The high pyroptosis-related risk score group of TCGA cohort was characterized by poorer prognosis (p < 0.001), with immune infiltration and function significantly decreased. For external validation, STS patients from Gene Expression Omnibus (GEO) were grouped according to the same cut-off point. The survival difference between two risk groups of GEO cohort was also significant (p < 0.001). With the combination of clinical characteristics, pyroptosis-related risk score was identified to serve as an independent prognostic factor for STS patients. In conclusion, this study provided a comprehensive overview of PRGs in STS and the potential role in prognosis, which could be an important direction for future studies.

软组织肉瘤（STS）构成了一类罕见且异质性的恶性肿瘤，其在治疗上面临着巨大的挑战。细胞焦亡已被证实与肿瘤的进展和预后密切相关。然而，目前尚无研究阐明细胞焦亡相关基因（PRGs）在STS中的作用。在本研究中，我们对STS中PRGs的基因表达谱进行了全面而系统的分析。利用癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库，我们确定了差异表达的PRGs。总共有34个PRGs在STS与正常组织之间存在异常表达。通过实时定量PCR（RT-qPCR）验证了几个PRGs。基于PRGs的共识聚类分析将STS患者分为两组，两组之间观察到显著的生存差异（p = 0.019）。在细胞焦亡相关簇之间确定了差异表达基因（DEGs）。基于最小绝对收缩和选择算子（LASSO）COX回归分析，构建了包含五个关键DEGs的细胞焦亡相关基因特征。TCGA队列中高细胞焦亡相关风险评分组表现出较差的预后（p < 0.001），其免疫浸润和功能显著降低。为了外部验证，根据相同的截止点将GEO数据库中的STS患者分组。GEO队列中两个风险组之间的生存差异也具有统计学意义（p < 0.001）。结合临床特征，细胞焦亡相关风险评分被确定为STS患者的独立预后因素。总之，本研究对STS中的PRGs及其在预后中的潜在作用提供了全面的概述，这可能是未来研究的重要方向。