Identify critical genes of breast cancer and corresponding leading natural product compounds of potential therapeutic targets.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2024-12-10 DOI:10.1007/s11030-024-11035-z

Xiaokai Fan, Le Xin, Xuan Yu, Maoxuan Liu, Joong Sup Shim, Gui Yang, Liang Chen

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引用次数: 0

Abstract

Breast cancer is a leading cause of cancer mortality among women globally, with over 2.26 million new cases annually, according to GLOBOCAN 2020. This accounts for approximately 25% of all new female cancers and 15.5% of female cancer deaths. To address this critical public health challenge, we conducted a multi-omics study aimed at identifying hub genes, therapeutic targets, and potential natural product-based therapies. We employed weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to pinpoint hub genes in breast cancer. Regulatory networks for these genes were constructed by re-analyzing chromatin immunoprecipitation sequencing (ChIP-seq) data from breast cancer cell lines. Additionally, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were utilized to characterize hub gene expression profiles and their relationships with immune cell clusters and tumor microenvironments. Survival analysis based on mRNA and protein expression levels identified prognostic factors and potential therapeutic targets. Lastly, large-scale virtual screening of natural product compounds revealed leading compounds that target squalene epoxidase (SQLE). Our multi-omics analysis paves the way for more effective clinical treatments for breast cancer.

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根据 GLOBOCAN 2020 的数据，乳腺癌是全球女性癌症死亡的主要原因，每年新增病例超过 226 万。这约占所有新发女性癌症的 25%，占女性癌症死亡人数的 15.5%。为了应对这一严峻的公共卫生挑战，我们开展了一项多组学研究，旨在确定枢纽基因、治疗靶点和潜在的天然产物疗法。我们采用加权基因共表达网络分析（WGCNA）和差异基因表达分析来确定乳腺癌的中心基因。通过重新分析乳腺癌细胞系的染色质免疫沉淀测序（ChIP-seq）数据，构建了这些基因的调控网络。此外，还利用单细胞 RNA 测序（scRNA-seq）和空间转录组学（ST）来描述中心基因的表达谱及其与免疫细胞集群和肿瘤微环境的关系。基于 mRNA 和蛋白质表达水平的生存分析确定了预后因素和潜在的治疗靶点。最后，对天然产物化合物进行大规模虚拟筛选，发现了针对角鲨烯环氧化物酶（SQLE）的主要化合物。我们的多组学分析为更有效的乳腺癌临床治疗铺平了道路。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;