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文章:

核糖体生物合成支撑肿瘤进展:一项用于生存与免疫治疗反应预测的综合特征

Ribosome Biogenesis Underpins Tumor Progression: A Comprehensive Signature for Survival and Immunotherapy Response Prediction

原文发布日期:5 August 2025

DOI: 10.3390/cancers17152576

类型: Article

开放获取: 是

 

英文摘要:

Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes.Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis.Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors.Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy.

 

摘要翻译: 

背景:核糖体生物合成(RiBi)是细胞增殖不可或缺的环节,其失调日益被认为是侵袭性癌症的标志之一。本研究旨在开发并验证一个反映多种肿瘤类型中RiBi活性的综合“PanRibo-515评分”,评估其预后意义,并探讨其与免疫检查点治疗结果的关系。 方法:我们筛选出515个RiBi相关基因(PanRibo-515),在训练数据集(GSE202203)上采用基于LASSO回归的策略,筛选出68个与预后最相关的基因子集(OncoRibo-68)。根据LASSO系数的正负号,为每个基因分配方向性(对生存的正面或负面影响)。我们结合前向选择方法,确定了一个用于计算OncoRibo-68评分的精炼基因子集。为进行验证,将癌症基因组图谱(TCGA)中的患者按OncoRibo-68评分高低分层,进行生存分析。此外,利用用于免疫治疗反应分析的生物信息学平台,对免疫治疗反应进行了额外验证。 结果:在多种癌症中,较高的OncoRibo-68评分始终与较差的总生存期和无进展生存期相关。升高的OncoRibo-68评分与免疫抑制性肿瘤微环境相关,但有趣的是,也与对检查点抑制剂反应增强相关。 结论:我们的研究结果强调了RiBi作为肿瘤侵袭性的重要决定因素,并确定OncoRibo-68评分是一个有前景的风险分层和治疗选择的生物标志物。未来的研究可以评估靶向RiBi通路是否能提高治疗效果,特别是与免疫治疗联合使用时。

 

 

原文链接:

Ribosome Biogenesis Underpins Tumor Progression: A Comprehensive Signature for Survival and Immunotherapy Response Prediction

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