Liu Po-Wu, Liu Zhao-Yi, Deng Shi-Jia, Zhang Xiu, Wang Zhi-Bin, Wu Na-Yiyuan, Liu Chao-Shui, Hu Ming-Hua, Wang Jing, Li He
University of South China, Hengyang Medical School, Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang, Hunan, 421001, People's Republic of China.
Hunan Clinical Research Center in Gynecologic Cancer, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, 410013, People's Republic of China.
Onco Targets Ther. 2025 Apr 23;18:585-601. doi: 10.2147/OTT.S491130. eCollection 2025.
Multiple studies have suggested that lncRNAs and pyroptosis play important roles in ovarian cancer (OC). However, the function of pyroptosis-related lncRNAs (PRLs) in OC is not fully understood.
Clinical information and RNA-seq data of OC patients (n = 379) were collected from TCGA database. Pearson correlation analysis and univariate Cox analysis were performed to identify prognostic PRLs, respectively. LASSO-COX regression was utilized to construct a prognostic PRLs signature. Kaplan-Meier (K-M) curve analyses and receiver operating characteristics (ROC) were used to evaluate the prognostic prediction of the signature. The association between risk score and tumor microenvironment infiltration, immunotherapy response and chemotherapy sensitivity were also analyzed. In addition, the function of TYMSOS on OC and pyroptosis was experimentally confirmed in cell lines.
Firstly, 32 prognostic PRLs were identified, and a novel prognostic PRLs signature was constructed and validated. Surprisingly, the prognostic PRLs signature could solidly predict the clinical outcome of patients with OC and patients with high-risk score shown a short overall survival. GSEA results suggested that the RPLs were mainly enriched in the inflammatory response pathway, p53 pathway, TGF-β signaling and TNFα signaling. Besides, our results demonstrated that the risk score was significantly associated with patients with immune infiltration, immunotherapy response and the sensitivity of veliparib and metformin. Furthermore, the oncogene effect of TYMSOS on OC by inhibiting pyroptosis was verified by experiments.
This study found that the prognostic PRLs signature may serve as an efficient biomarker in predicting the prognosis, tumor microenvironment infiltration, and sensitivity of chemotherapeutic agents. TYMSOS is a potential biomarker in OC, and it might promote tumor progression by inhibiting pyroptosis.
多项研究表明，长链非编码RNA（lncRNAs）和细胞焦亡在卵巢癌（OC）中发挥重要作用。然而，细胞焦亡相关lncRNAs（PRLs）在OC中的功能尚未完全明确。
从TCGA数据库收集OC患者（n = 379）的临床信息和RNA测序数据。分别进行Pearson相关分析和单因素Cox分析以鉴定预后PRLs。利用LASSO - COX回归构建预后PRLs特征。采用Kaplan - Meier（K - M）曲线分析和受试者工作特征（ROC）评估该特征的预后预测能力。还分析了风险评分与肿瘤微环境浸润、免疫治疗反应和化疗敏感性之间的关联。此外，在细胞系中通过实验证实了TYMSOS对OC和细胞焦亡的作用。
首先，鉴定出32个预后PRLs，并构建和验证了一种新的预后PRLs特征。令人惊讶的是，该预后PRLs特征能够可靠地预测OC患者的临床结局，高风险评分患者的总生存期较短。基因集富集分析（GSEA）结果表明，PRLs主要富集于炎症反应通路、p53通路、转化生长因子 - β（TGF - β）信号通路和肿瘤坏死因子α（TNFα）信号通路。此外，我们的结果表明，风险评分与免疫浸润患者、免疫治疗反应以及维利帕尼和二甲双胍的敏感性显著相关。此外，通过实验验证了TYMSOS通过抑制细胞焦亡对OC的致癌作用。
本研究发现，预后PRLs特征可能作为一种有效的生物标志物，用于预测预后、肿瘤微环境浸润和化疗药物敏感性。TYMSOS是OC中的一种潜在生物标志物，它可能通过抑制细胞焦亡促进肿瘤进展。
