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基于机器学习识别弥漫性大B细胞淋巴瘤中与铜死亡相关的长链非编码RNA生物标志物

Machine learning-based identification of cuproptosis-related lncRNA biomarkers in diffuse large B-cell lymphoma.

作者信息

Ouyang Wenhao, Lai Zijia, Huang Hong, Ling Li

机构信息

Department of Neurology, Shenzhen Hospital, Southern Medical University, No.1333 Xinhu Road, Shenzhen, 518000, Guangdong, China.

Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.

出版信息

Cell Biol Toxicol. 2025 Apr 21;41(1):72. doi: 10.1007/s10565-025-10030-w.

Abstract

Multiple machine learning techniques were employed to identify key long non-coding RNA (lncRNA) biomarkers associated with cuproptosis in Diffuse Large B-Cell Lymphoma (DLBCL). Data from the TCGA and GEO databases facilitated the identification of 126 significant cuproptosis-related lncRNAs. Various feature selection methods, such as Univariate Filtering, Lasso, Boruta, and Random Forest, were integrated with a Transformer-based model to develop a robust prognostic tool. This model, validated through fivefold cross-validation, demonstrated high accuracy and robustness in predicting risk scores. MALAT1 was pinpointed using permutation feature importance from machine learning methods and was further validated in DLBCL cell lines, confirming its substantial role in cell proliferation. Knockdown experiments on MALAT1 led to reduced cell proliferation, underscoring its potential as a therapeutic target. This integrated approach not only enhances the precision of biomarker identification but also provides a robust prognostic model for DLBCL, demonstrating the utility of these lncRNAs in personalized treatment strategies. This study highlights the critical role of combining diverse machine learning methods to advance DLBCL research and develop targeted cancer therapies.

摘要

采用多种机器学习技术来识别与弥漫性大B细胞淋巴瘤(DLBCL)中的铜死亡相关的关键长链非编码RNA(lncRNA)生物标志物。来自TCGA和GEO数据库的数据有助于识别126种与铜死亡相关的重要lncRNA。各种特征选择方法,如单变量过滤、套索、Boruta和随机森林,与基于Transformer的模型相结合,以开发一种强大的预后工具。该模型通过五折交叉验证进行验证,在预测风险评分方面表现出高准确性和稳健性。使用机器学习方法的排列特征重要性确定了MALAT1,并在DLBCL细胞系中进一步验证,证实了其在细胞增殖中的重要作用。对MALAT1的敲低实验导致细胞增殖减少,突出了其作为治疗靶点的潜力。这种综合方法不仅提高了生物标志物识别的精度,还为DLBCL提供了一个强大的预后模型,证明了这些lncRNA在个性化治疗策略中的实用性。这项研究强调了结合多种机器学习方法对推进DLBCL研究和开发靶向癌症治疗的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9561/12011908/db52ed6562c7/10565_2025_10030_Fig1_HTML.jpg

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