A Pyroptosis-Related LncRNA Signature for Predicting Prognosis, Immune Features and Drug Sensitivity in Ovarian Cancer.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-04-23 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S491130

Po-Wu Liu, Zhao-Yi Liu, Shi-Jia Deng, Xiu Zhang, Zhi-Bin Wang, Na-Yiyuan Wu, Chao-Shui Liu, Ming-Hua Hu, Jing Wang, He Li

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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一个预测卵巢癌预后、免疫特征和药物敏感性的焦热相关LncRNA标记。

背景：多项研究表明lncrna和焦亡在卵巢癌（OC）中发挥重要作用。然而，与热降解相关的lncRNAs （prl）在OC中的功能尚不完全清楚。方法：从TCGA数据库中收集379例OC患者的临床资料和RNA-seq数据。分别采用Pearson相关分析和单变量Cox分析来确定预后prl。利用LASSO-COX回归构建预后prl特征。采用Kaplan-Meier （K-M）曲线分析和受试者工作特征（ROC）评价该特征的预后预测。分析风险评分与肿瘤微环境浸润、免疫治疗反应和化疗敏感性的关系。此外，TYMSOS在细胞系中对OC和焦亡的作用也得到了实验证实。结果：首先，鉴定出32个预后prl，构建并验证了一个新的预后prl特征。令人惊讶的是，预后prl特征可以可靠地预测OC患者的临床结局，高危评分患者的总生存期较短。GSEA结果提示RPLs主要富集于炎症反应通路、p53通路、TGF-β信号通路和tnf - α信号通路。此外，我们的研究结果表明，风险评分与患者的免疫浸润、免疫治疗反应以及维利帕里和二甲双胍的敏感性显著相关。此外，通过实验验证了TYMSOS对OC的抑癌作用。结论：本研究发现预后prl标记可作为预测预后、肿瘤微环境浸润及化疗药物敏感性的有效生物标志物。TYMSOS是一种潜在的OC生物标志物，它可能通过抑制焦亡来促进肿瘤进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.