单细胞分辨率下肺腺癌转移代谢驱动基因的鉴定和靶向药物筛选。

IF 1.7 4区 医学 Q4 ONCOLOGY
Translational cancer research Pub Date : 2025-08-31 Epub Date: 2025-08-28 DOI:10.21037/tcr-2025-484
Liang Wu, Wenjuan Zhao, Xin Guo, Zuquan Hu, Sen Chen, Wenzhu Huang
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引用次数: 0

摘要

背景:肺腺癌(LUAD)是肺癌的主要类型,转移是导致预后不良和死亡的主要原因。代谢激活是肿瘤转移的重要驱动因素;然而,单细胞水平的代谢异质性对靶向代谢相关基因进行治疗提出了重大挑战。本研究旨在解码肿瘤转移过程中的代谢驱动因素,优化LUAD预后预测,筛选特异性靶向药物。方法:在本研究中,我们确定在LUAD转移过程中,微环境中肿瘤和免疫细胞的代谢激活显著改变。同时,我们基于单细胞rna测序(scRNA-seq)数据确定了关键代谢驱动基因(mdg),这些基因可以作为靶向治疗的靶点。然后,我们构建了一个基于mdg的新型预测风险模型,并在独立数据集上验证了其出色的预测性能。采用非负矩阵分解(NMF)算法,根据mdg将LUAD分子亚型分为三类,并评估其与预后和临床特征的相关性。结果:我们筛选了307种靶向mdg的药物,并证实了胆酸作为筛选小组中的代表性化合物对LUAD细胞迁移的抑制作用。结论:我们的研究为转移性LUAD的代谢相关基因治疗提供了潜在的靶点和候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of metabolic driver genes and targeted drug screening for lung adenocarcinoma metastasis at the single-cell resolution.

Background: Lung adenocarcinoma (LUAD) is the predominant type of lung cancer, and metastasis is a major cause of poor prognosis and death. Metabolic activation is a crucial factor driving tumor metastasis; however, the metabolic heterogeneity at the single-cell level presents significant challenges in targeting metabolism-related genes for treatment. This study aimed to decode the metabolic drivers in tumor metastasis progression to optimize LUAD prognosis prediction and screen specific targeted drugs.

Methods: In this study, we determined that the metabolic activation of tumor and immune cells in the microenvironment is significantly altered during LUAD metastasis. Simultaneously, we identify pivotal metabolic driver genes (MDGs) based on single-cell RNA-sequencing (scRNA-seq) data, which could serve as targets for targeted therapy. We then constructed a novel prognostic risk model based on MDGs and validated its excellent predictive performance in independent datasets. Using the non-negative matrix factorization (NMF) algorithm, we classify LUAD molecular subtypes into three clusters according to MDGs and evaluate their association with prognosis and clinical characteristics.

Results: We screened a panel of 307 drugs targeting MDGs and confirmed the efficacy of cholic acid, as a representative compound from the screened panel, in inhibiting the migration of LUAD cells.

Conclusions: Our research provides potential targets and candidate drug for targeting metabolic-related genes in metastatic LUAD treatment.

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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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