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磷脂酶A2γ4a(PLA2G4A)对各种癌症预后影响的多组学分析及其在乳腺癌细胞系中的实验验证

Multi-omics analysis of the effects of pla2g4a on the prognosis of various cancers and its experimental validation in breast cancer cell lines.

作者信息

Qian Yao, Yuan Quan, Yu Hao, Ye Rongjie, Niu Ming, Liu Feng

机构信息

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150000, Heilongjiang, China.

Department of Hepato-Biliary-Pancreatic and Vascular Surgery, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361000, Fujian, China.

出版信息

Discov Oncol. 2025 Jul 7;16(1):1278. doi: 10.1007/s12672-025-03118-6.

DOI:10.1007/s12672-025-03118-6
PMID:40624348
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12234970/
Abstract

BACKGROUND

Platelet-related exosomes (PREs) are microparticles secreted by platelets into the bloodstream and are implicated in various cancer processes. This study aims to identify critical genes involved in Breast Cancer (BC)-associated PREs and to evaluate their role in cancer prognosis. PLA2G4A was identified as a key gene through the use of machine learning techniques and various genomic analyses, providing a foundation for precision medicine in BC treatment.

METHODS

Download cancer-related data from databases such as UCSC Xena and ExMdb, use LASSO Cox regression and various machine learning algorithms to screen genes associated with BC survival, and perform functional and pathway enrichment analysis. The expression, immune relevance, diagnostic efficacy, and drug sensitivity of the PLA2G4A gene in pan-cancer and BC were specifically analyzed. The function of PLA2G4A in BC was validated through experiments, and its drug response and molecular docking were predicted using various databases and software tools.

RESULTS

Machine learning methods and LASSO Cox regression were applied to analyze the relationship between gene expression and BC survival. PLA2G4A was identified as a key gene associated with cancer prognosis, supported by analyses of differential gene expression, survival outcomes, single nucleotide variations (SNVs), and copy number variations (CNVs). Biological pathway analyses through KEGG, GO, and GSEA highlighted PLA2G4A's involvement in key cancer-related processes. In vitro studies, including cell scratch assays, Transwell migration assays, and EdU proliferation tests, demonstrated that overexpression of PLA2G4A inhibited the proliferation and migration of BC cells.

CONCLUSIONS

PLA2G4A plays a crucial role in the progression of BC, acting as a potential tumor-suppressor gene. The findings support its potential as a prognostic biomarker and further investigation is needed to explore its therapeutic potential in clinical settings.

摘要

背景

血小板相关外泌体(PREs)是血小板分泌到血液中的微粒,与多种癌症进程有关。本研究旨在鉴定参与乳腺癌(BC)相关PREs的关键基因,并评估它们在癌症预后中的作用。通过使用机器学习技术和各种基因组分析,PLA2G4A被鉴定为关键基因,为BC治疗中的精准医学提供了基础。

方法

从UCSC Xena和ExMdb等数据库下载癌症相关数据,使用LASSO Cox回归和各种机器学习算法筛选与BC生存相关的基因,并进行功能和通路富集分析。具体分析了PLA2G4A基因在泛癌和BC中的表达、免疫相关性、诊断效能和药物敏感性。通过实验验证了PLA2G4A在BC中的功能,并使用各种数据库和软件工具预测了其药物反应和分子对接。

结果

应用机器学习方法和LASSO Cox回归分析基因表达与BC生存之间的关系。通过差异基因表达、生存结果、单核苷酸变异(SNV)和拷贝数变异(CNV)分析,PLA2G4A被鉴定为与癌症预后相关的关键基因。通过KEGG、GO和GSEA进行的生物通路分析突出了PLA2G4A参与关键的癌症相关进程。包括细胞划痕试验、Transwell迁移试验和EdU增殖试验在内的体外研究表明,PLA2G4A的过表达抑制了BC细胞的增殖和迁移。

结论

PLA2G4A在BC进展中起关键作用,作为潜在的肿瘤抑制基因。这些发现支持了其作为预后生物标志物的潜力,需要进一步研究以探索其在临床环境中的治疗潜力。

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