四种与氧化应激相关的基因之一,预测生化无复发生存,促进前列腺癌的增殖和侵袭。

Q2 Biochemistry, Genetics and Molecular Biology Advances and Applications in Bioinformatics and Chemistry Pub Date : 2024-11-30 eCollection Date: 2024-01-01 DOI:10.2147/AABC.S489131
Peiqiang Wu, Jianlei Zhang, Li Guo, Bohong Chen, Lingxiao Xiong, Yuefeng Du
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引用次数: 0

摘要

背景:前列腺癌(PCa)的发展在很大程度上取决于氧化应激(OS)水平的升高和抗氧化系统的缺陷。识别与氧化应激相关的基因对于指导前列腺癌的治疗和未来的研究至关重要。方法:TCGA和GTEx数据库提供大量RNA-seq数据,GEO数据库提供单细胞数据GSE141445。利用活性氧(reactive oxygen species, ROS)标记,利用R包“Seurat”和“AUCell”进行氧化应激相关的单细胞分析和聚类鉴定。用“limma”R包鉴定正常和PCa样品中的差异表达基因(deg)。采用LASSO回归分析建立复发评分(recurrent score, RS)模型。采用R包“maftools”和CIBERSORT方法分别检测基因突变和浸润免疫细胞。随机森林分析后选择LAMP5进行进一步调查。结果:RS模型是PCa的独立预测因子。肿瘤免疫微环境和基因突变频率在高危评分组和低危评分组之间存在显著差异。进一步研究发现,在PC-3和DU145细胞系中,下调LAMP5可抑制细胞增殖和侵袭,这在体外实验中得到证实。结论:成功建立了鲁棒的RS模型。本研究结果表明,LAMP5可能参与前列腺癌细胞的增殖和侵袭。
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LAMP5, One of Four Genes Related to Oxidative Stress That Predict Biochemical Recurrence-Free Survival, Promotes Proliferation and Invasion in Prostate Cancer.

Background: Prostate cancer (PCa) development largely depends on increased levels of oxidative stress (OS) and a deficient anti-oxidative system. Identifying genes associated with oxidative stress is critical in order to direct PCa therapy and future research.

Methods: The TCGA and GTEx databases provided the bulk RNA-seq data, and the GEO database provided the single-cell data GSE141445. Utilizing reactive oxygen species (ROS) markers, single-cell analysis and cluster identification related to oxidative stress were conducted using the R packages "Seurat" and "AUCell". The differentially expressed genes (DEGs) in normal and PCa samples were identified with the "limma" R package. LASSO regression analysis was used to build a recurrence score (RS) model. The R packages "maftools" and the CIBERSORT method were employed to explore genetic mutation and the infiltrating immune cell, respectively. LAMP5 was chosen for further investigation after random forest analysis was performed.

Results: The RS model for PCa was found to be an independent predictor. The tumor immune microenvironment and the frequency of gene mutations differed significantly between the high- and low-risk score groups. Further investigation revealed that downregulation of LAMP5 in PC-3 and DU145 cell lines suppressed cell proliferation and invasion, as demonstrated by the results of in vitro experiments.

Conclusion: We successfully created a robust RS model. The result of the study indicates that LAMP5 could contribute to cell proliferation and invasion in PCa.

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来源期刊
Advances and Applications in Bioinformatics and Chemistry
Advances and Applications in Bioinformatics and Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
6.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊最新文献
Non-Invasive Cancer Detection Using Blood Test and Predictive Modeling Approach. Recent Applications of Artificial Intelligence in Discovery of New Antibacterial Agents. LAMP5, One of Four Genes Related to Oxidative Stress That Predict Biochemical Recurrence-Free Survival, Promotes Proliferation and Invasion in Prostate Cancer. Investigating the Potency of Erythrina‒Derived Flavonoids as Cholinesterase Inhibitors and Free Radical Scavengers Through in silico Approach: Implications for Alzheimer's Disease Therapy. Employing Hexahydroquinolines as PfCDPK4 Inhibitors to Combat Malaria Transmission: An Advanced Computational Approach.
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