Construction and verification of a prognostic model for bladder cancer based on disulfidptosis-related angiogenesis genes.

IF 2.4 3区 生物学 Q2 MULTIDISCIPLINARY SCIENCES PeerJ Pub Date : 2025-02-21 eCollection Date: 2025-01-01 DOI:10.7717/peerj.18911
Zhihao Zhou, Yuwei Zhang, Yuhua Zhou, Jiayu Gu, Jufa Li, Jianfeng Shao, Ninghan Feng
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Abstract

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system and one of the most common cancers worldwide. This study seeks to examine the influence of angiogenesis-related genes (ARGs) linked to disulfidptosis on BLCA patients and to formulate a prognostic model for evaluating their prognosis and response to immunotherapy.

Methods: This study used sequencing data of BLCA in the Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering analysis, cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis were used to screen hub genes and construct a related prognostic risk model. The receiver operating characteristic (ROC) curve and independent prognostic analysis were then used to verify the predictive performance of the signature genes. Clinical characteristics, immune status, and Tumor Mutation Burden (TMB) of the prognostic risk model were evaluated. The expression levels of model genes within standard bladder epithelial cell lines (SV-HUC-1) and bladder cancer cell lines (T24 and SW1710) were quantified through qRT-PCR.

Results: The constructed prognostic risk model can be used as an independent risk indicator for BLCA and was validated in an external dataset. Immune cell infiltration analysis showed that CD8+T cells, Tregs and dendritic cells were significantly different between the two groups. A significant increase was observed in the Stromal score, Immune score and ESTIMATE score in the high-risk group compared with the low-risk group. The Immune Exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score of the high-risk group were higher than those of the low-risk score group. Compared with the normal bladder epithelial cell line (SV-HUC-1), the expression levels of 2 model genes (COL5A2 and SCG2) in bladder cancer cell lines (T24 and SW1710) were significantly elevated.

Conclusion: This study helps us understand the characteristics of disulfidptosis-related subgroups. The characteristics of disulfidptosis-related ARGs may be used to evaluate the prognosis and immunotherapy response of BLCA patients.

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基于二硫化氢相关血管生成基因的膀胱癌预后模型的构建与验证。
背景:膀胱癌(BLCA)是泌尿系统最常见的恶性肿瘤,也是世界上最常见的癌症之一。本研究旨在研究血管生成相关基因(ARGs)对BLCA患者的影响,并建立一个预后模型来评估其预后和对免疫治疗的反应。方法:本研究使用肿瘤基因组图谱(TCGA)数据库中的BLCA测序数据。采用无监督共识聚类分析、cox回归分析、最小绝对收缩和选择算子(LASSO)回归分析筛选枢纽基因,构建相关预后风险模型。然后使用受试者工作特征(ROC)曲线和独立预后分析来验证特征基因的预测性能。评估预后风险模型的临床特征、免疫状态和肿瘤突变负担(Tumor Mutation Burden, TMB)。采用qRT-PCR方法定量模型基因在标准膀胱上皮细胞株(SV-HUC-1)和膀胱癌细胞株(T24和SW1710)中的表达水平。结果:构建的预后风险模型可作为BLCA的独立风险指标,并在外部数据集中得到验证。免疫细胞浸润分析显示,两组间CD8+T细胞、Tregs细胞和树突状细胞均有显著差异。高危组基质评分、免疫评分、ESTIMATE评分较低危组明显升高。高危组的免疫排斥评分和肿瘤免疫功能障碍与排斥(TIDE)评分高于低危组。与正常膀胱上皮细胞系(SV-HUC-1)相比,膀胱癌细胞系(T24和SW1710)中2个模式基因(COL5A2和SCG2)的表达水平显著升高。结论:本研究有助于我们了解二硫中毒相关亚群的特征。二硫枯相关ARGs的特征可用于评价BLCA患者的预后和免疫治疗反应。
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来源期刊
PeerJ
PeerJ MULTIDISCIPLINARY SCIENCES-
CiteScore
4.70
自引率
3.70%
发文量
1665
审稿时长
10 weeks
期刊介绍: PeerJ is an open access peer-reviewed scientific journal covering research in the biological and medical sciences. At PeerJ, authors take out a lifetime publication plan (for as little as $99) which allows them to publish articles in the journal for free, forever. PeerJ has 5 Nobel Prize Winners on the Board; they have won several industry and media awards; and they are widely recognized as being one of the most interesting recent developments in academic publishing.
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