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通过对分类应激源的基因反应进行聚类来增强癌症治疗和理解。

Enhancing cancer treatment and understanding through clustering of gene responses to categorical stressors.

机构信息

Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.

Cancer and Metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.

出版信息

Sci Rep. 2023 Apr 21;13(1):6517. doi: 10.1038/s41598-023-33785-w.

DOI:10.1038/s41598-023-33785-w
PMID:37085609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10121664/
Abstract

Cancer cells have a unique metabolic activity in the glycolysis pathway compared to normal cells, which allows them to maintain their growth and proliferation. Therefore, inhibition of glycolytic pathways may be a promising therapeutic approach for cancer treatment. In this novel study, we analyzed the genetic responses of cancer cells to stressors, particularly to drugs that target the glycolysis pathway. Gene expression data for experiments on different cancer cell types were extracted from the Gene Expression Omnibus and the expression fold change was then clustered after dimensionality reduction. We identified four groups of responses: the first and third were most affected by anti-glycolytic drugs, especially those acting on multiple pathways at once, and consisted mainly of squamous and mesenchymal tissues, showing higher mitotic inhibition and apoptosis. The second and fourth groups were relatively unaffected by treatment, comprising mainly gynecologic and hormone-sensitive groups, succumbing least to glycolysis inhibitors. Hexokinase-targeted drugs mainly showed this blunted effect on cancer cells. This study highlights the importance of analyzing the molecular states of cancer cells to identify potential targets for personalized cancer therapies and to improve our understanding of the disease.

摘要

与正常细胞相比,癌细胞在糖酵解途径中具有独特的代谢活性,这使得它们能够维持生长和增殖。因此,抑制糖酵解途径可能是癌症治疗的一种有前途的治疗方法。在这项新的研究中,我们分析了癌细胞对压力源的遗传反应,特别是针对糖酵解途径的药物。从基因表达综合数据库中提取了不同癌症细胞类型的实验基因表达数据,然后在降维后对表达倍数变化进行聚类。我们确定了四种反应类型:第一组和第三组受抗糖酵解药物的影响最大,特别是那些同时作用于多个途径的药物,主要由鳞状和间充质组织组成,表现出更高的有丝分裂抑制和细胞凋亡。第二组和第四组受治疗的影响相对较小,主要由妇科和激素敏感组组成,对糖酵解抑制剂的抵抗力最低。己糖激酶靶向药物主要对癌细胞表现出这种钝化作用。这项研究强调了分析癌细胞分子状态的重要性,以确定个性化癌症治疗的潜在靶点,并加深对该疾病的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/7d10e7e278ea/41598_2023_33785_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/f0748ed67dfc/41598_2023_33785_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/ba6d4959a907/41598_2023_33785_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/805d51ae4499/41598_2023_33785_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/7660d4bbf6e1/41598_2023_33785_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/7d10e7e278ea/41598_2023_33785_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/f0748ed67dfc/41598_2023_33785_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/ba6d4959a907/41598_2023_33785_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/805d51ae4499/41598_2023_33785_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/7660d4bbf6e1/41598_2023_33785_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a331/10121664/7d10e7e278ea/41598_2023_33785_Fig5_HTML.jpg

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本文引用的文献

1
Glycolysis in tumor microenvironment as a target to improve cancer immunotherapy.肿瘤微环境中的糖酵解作为改善癌症免疫治疗的靶点。
Front Cell Dev Biol. 2022 Sep 19;10:1013885. doi: 10.3389/fcell.2022.1013885. eCollection 2022.
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simplifyEnrichment: A Bioconductor Package for Clustering and Visualizing Functional Enrichment Results.simplifyEnrichment:一个用于聚类和可视化功能富集结果的 Bioconductor 包。
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Polygenic and Network-based studies in risk identification and demystification of cancer.
基于多基因和网络的癌症风险识别与揭秘研究。
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Glycolysis Changes the Microenvironment and Therapeutic Response Under the Driver of Gene Mutation in Esophageal Adenocarcinoma.糖酵解在食管腺癌基因突变驱动下改变微环境和治疗反应。
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Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.自分泌 TGF-β 在癌症中的作用:文献综述及实验分析中的注意事项。
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cola: an R/Bioconductor package for consensus partitioning through a general framework.cola:一个通过通用框架进行共识分割的 R/Bioconductor 包。
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Detection of immunogenic cell death and its relevance for cancer therapy.免疫原性细胞死亡的检测及其与癌症治疗的相关性。
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Cell Reversal From a Differentiated to a Stem-Like State at Cancer Initiation.在癌症起始阶段细胞从分化状态逆转为干细胞样状态。
Front Oncol. 2020 Apr 15;10:541. doi: 10.3389/fonc.2020.00541. eCollection 2020.
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mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges.癌症中的mTOR信号通路与mTOR抑制剂:进展与挑战
Cell Biosci. 2020 Mar 10;10:31. doi: 10.1186/s13578-020-00396-1. eCollection 2020.
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Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy.靶向葡萄糖代谢抑制肿瘤进展:抗糖酵解肿瘤治疗的前景。
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