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基于机器学习的乳酸化相关基因LILRB4预测前列腺癌的预后及免疫治疗效果

Lactylation-Related Gene LILRB4 Predicts the Prognosis and Immunotherapy of Prostate Cancer Based on Machine Learning.

作者信息

Wang Qinghua, Qin Xin, Zhao Yan, Jiang Wei, Xu Mingming, Li Xilei, Li Haopeng, Zhou Juan, Wu Gang

机构信息

Department of Urology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of ICU, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

J Cell Mol Med. 2025 Jun;29(12):e70669. doi: 10.1111/jcmm.70669.

DOI:10.1111/jcmm.70669
PMID:40576161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12203412/
Abstract

Lactylation plays a pivotal role in the metabolic reprogramming, proliferation, migration and immune evasion of tumour cells. However, its specific impact on prostate cancer (PCa) remains poorly understood. This study aimed to investigate the role of lactylation related genes (LRGs) in PCa. LRGs were identified and analysed using data from The Cancer Genome Atlas (TCGA), DKFZ2018, GSE46602 and GSE70768 cohorts. Unsupervised clustering was employed to categorise patients with PCa into two distinct clusters. Prognostic models for PCa were developed using multiple machine learning techniques. LRGs signature was established and validated through training and validation sets. The role of leukocyte immunoglobulin-like receptor B4 (LILRB4) in PCa was examined both in vitro and in vivo. Analysis of LRG expression and prognosis in patients with PCa revealed two distinct clusters with differing survival rates and immune responses. Machine learning models demonstrated the ability to predict survival risks, potentially aiding in the development of personalised treatment strategies. Additionally, LILRB4, a key LRG, promotes PCa progression by modulating the NF-κB and PI3K/AKT pathways, highlighting its potential as a therapeutic target. LRGs exert a pivotal influence on PCa, impacting patient prognosis, immune response and drug sensitivity. The LRGs signature emerges as an essential prognostic tool and a promising therapeutic target for PCa.

摘要

乳酰化在肿瘤细胞的代谢重编程、增殖、迁移和免疫逃逸中起关键作用。然而,其对前列腺癌(PCa)的具体影响仍知之甚少。本研究旨在探讨乳酰化相关基因(LRGs)在PCa中的作用。利用来自癌症基因组图谱(TCGA)、DKFZ2018、GSE46602和GSE70768队列的数据对LRGs进行识别和分析。采用无监督聚类将PCa患者分为两个不同的簇。使用多种机器学习技术建立PCa的预后模型。通过训练集和验证集建立并验证LRGs特征。在体外和体内研究了白细胞免疫球蛋白样受体B4(LILRB4)在PCa中的作用。对PCa患者LRG表达和预后的分析揭示了两个不同的簇,其生存率和免疫反应不同。机器学习模型显示出预测生存风险的能力,可能有助于制定个性化治疗策略。此外,关键的LRG LILRB4通过调节NF-κB和PI3K/AKT途径促进PCa进展,突出了其作为治疗靶点的潜力。LRGs对PCa产生关键影响,影响患者预后、免疫反应和药物敏感性。LRGs特征成为PCa重要的预后工具和有前景的治疗靶点。

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本文引用的文献

1
Immune Checkpoints in B Cells: Unlocking New Potentials in Cancer Treatment.B细胞中的免疫检查点:开启癌症治疗的新潜力
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Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials.乳酰化在癌症中的作用:肿瘤生物学中的机制和治疗潜力。
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Low level exposure to BDE-47 facilitates the development of prostate cancer through TOP2A/LDHA/lactylation positive feedback circuit.低水平暴露于 BDE-47 通过 TOP2A/LDHA/乳酰化正反馈回路促进前列腺癌的发展。
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Lactate/lactylation in ocular development and diseases.乳酸/乳酰化在眼部发育和疾病中的作用
Trends Mol Med. 2024 Jul 24. doi: 10.1016/j.molmed.2024.07.001.
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LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway.LILRB4 通过 STAT3-PFKFB1 通路调节多发性骨髓瘤的发展。
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Citation classic: distribution-free estimation of age-related centiles, by Healy, Rasbash and Yang (1988).经典文献引用:希利、拉斯巴什和杨(1988年)所著的《与年龄相关的百分位数的无分布估计》
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NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.高效的DNA修复和化疗耐药性需要NBS1乳酸化。
Nature. 2024 Jul;631(8021):663-669. doi: 10.1038/s41586-024-07620-9. Epub 2024 Jul 3.
9
LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.LILRB4 在多发性骨髓瘤细胞中通过 p-SHP2/NF-κB/RELT 信号通路促进骨病变。
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10
SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.SLC4A4 是前列腺癌中恩扎鲁胺耐药的新型驱动基因。
Cancer Lett. 2024 Aug 10;597:217070. doi: 10.1016/j.canlet.2024.217070. Epub 2024 Jun 14.