用于预测浆液性卵巢癌预后的新型程序性细胞死亡相关基因特征

IF 3.8 3区 医学 Q1 REPRODUCTIVE BIOLOGY Journal of Ovarian Research Pub Date : 2024-04-29 DOI:10.1186/s13048-024-01419-y
Feng Zhan, Yina Guo, Lidan He
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引用次数: 0

摘要

本研究旨在通过单细胞RNA测序(scRNA-seq)探讨差异表达的程序性细胞死亡基因(DEPCDGs)对浆液性卵巢癌(SOC)异质性的贡献,并评估其作为临床预后预测因子的潜力。SOC的scRNA-seq数据是从基因表达总库(Gene Expression Omnibus)数据库中提取的,采用主成分分析法进行细胞聚类。大量RNA-seq数据用于分析SOC相关免疫细胞亚群的关键基因。利用 CIBERSORT 和单样本基因组富集分析(ssGSEA)计算免疫细胞得分。通过单变量和多变量 Cox 分析建立了预后模型和提名图。我们的分析发现,48个DEPCDGs与细胞凋亡信号转导和氧化应激通路显著相关,并通过生存分析确定了7个关键DEPCDGs(CASP3、GADD45B、GNA15、GZMB、IL1B、ISG20和RHOB)。此外,还利用 scRNA-seq 鉴定了八种不同的细胞亚型。研究发现,G蛋白亚基α15(GNA15)在这些亚型中的表达量较低,且与免疫细胞有密切联系。根据 GNA15 高表达组和低表达组所确定的 DEGs,构建了一个由 8 个具有显著预后价值的基因组成的预后模型,可有效预测患者的总生存期。此外,还开发了一个包含 RS 特征、年龄、分级和分期的提名图,并利用两个大型 SOC 数据集进行了验证。GNA15 成为了 SOC 患者独立且优秀的预后标志物。这项研究为 DEPCDGs 在 SOC 中的预后潜力提供了宝贵的见解,为个性化治疗策略提供了新的途径。
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A novel defined programmed cell death related gene signature for predicting the prognosis of serous ovarian cancer
This study aims to explore the contribution of differentially expressed programmed cell death genes (DEPCDGs) to the heterogeneity of serous ovarian cancer (SOC) through single-cell RNA sequencing (scRNA-seq) and assess their potential as predictors for clinical prognosis. SOC scRNA-seq data were extracted from the Gene Expression Omnibus database, and the principal component analysis was used for cell clustering. Bulk RNA-seq data were employed to analyze SOC-associated immune cell subsets key genes. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were utilized to calculate immune cell scores. Prognostic models and nomograms were developed through univariate and multivariate Cox analyses. Our analysis revealed that 48 DEPCDGs are significantly correlated with apoptotic signaling and oxidative stress pathways and identified seven key DEPCDGs (CASP3, GADD45B, GNA15, GZMB, IL1B, ISG20, and RHOB) through survival analysis. Furthermore, eight distinct cell subtypes were characterized using scRNA-seq. It was found that G protein subunit alpha 15 (GNA15) exhibited low expression across these subtypes and a strong association with immune cells. Based on the DEGs identified by the GNA15 high- and low-expression groups, a prognostic model comprising eight genes with significant prognostic value was constructed, effectively predicting patient overall survival. Additionally, a nomogram incorporating the RS signature, age, grade, and stage was developed and validated using two large SOC datasets. GNA15 emerged as an independent and excellent prognostic marker for SOC patients. This study provides valuable insights into the prognostic potential of DEPCDGs in SOC, presenting new avenues for personalized treatment strategies.
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来源期刊
Journal of Ovarian Research
Journal of Ovarian Research REPRODUCTIVE BIOLOGY-
CiteScore
6.20
自引率
2.50%
发文量
125
审稿时长
>12 weeks
期刊介绍: Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.
期刊最新文献
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