Discovery of anticancer targets for triple-negative breast cancer through comparative analysis of gene dependency score

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology and Bioprocess Engineering Pub Date : 2024-08-14 DOI:10.1007/s12257-024-00138-x
Bo Kyung Kim, Gahee Kim, Wonhee Hur, Yoojin Choi, Suhyun Hwangbo, Jae Yong Ryu
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Abstract

Patients with triple-negative breast cancer (TNBC) often face an unfavorable prognosis due to the lack of targeted therapy. Thus, identifying drug targets specific to the TNBC subtype is crucial for effective treatment. Here, we propose a strategy to identify potential inhibitory targets specific to this subtype based on the gene dependency score (GDS), a quantitative measure of essentiality of each gene determined in cancer cell lines. Specifically, we compared the GDS values of 17,387 genes among cell lines of four breast cancer (BC) subtypes, namely luminal A, luminal B, HER2-positive, and TNBC, to identify genes showing specific essentiality in TNBC subtype cell lines. Twenty-two genes were predicted as potential inhibitory targets. Of these, we selected two genes, ILK and RHOA, based on survival analysis conducted across the four BC subtypes. We propose these two genes as potential biomarkers for TNBC. Furthermore, we experimentally validated that inhibiting ILK expression with a specific inhibitor reduced cell viability more in TNBC subtype cell lines than in other BC subtype cell lines. Therefore, ILK is a potential drug target specific to TNBC. The strategy proposed is expected to be useful in identifying biomarker and therapeutic target genes in not only BC but also other cancers.

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通过基因依赖性评分比较分析发现三阴性乳腺癌的抗癌靶点
由于缺乏靶向治疗,三阴性乳腺癌(TNBC)患者的预后往往很差。因此,确定 TNBC 亚型的特异性药物靶点对有效治疗至关重要。在此,我们提出了一种基于基因依赖性评分(GDS)的策略,以确定该亚型的潜在特异性抑制靶点,基因依赖性评分是对癌细胞系中每个基因的重要程度的定量测量。具体来说,我们比较了四种乳腺癌(BC)亚型(即管腔A型、管腔B型、HER2阳性和TNBC)细胞系中17,387个基因的GDS值,以确定在TNBC亚型细胞系中表现出特异性本质的基因。22个基因被预测为潜在的抑制靶点。其中,我们根据对四种 BC 亚型进行的存活率分析选出了 ILK 和 RHOA 这两个基因。我们建议将这两个基因作为 TNBC 的潜在生物标志物。此外,我们还通过实验验证了用特异性抑制剂抑制ILK的表达比抑制其他BC亚型细胞株更能降低TNBC亚型细胞株的细胞活力。因此,ILK是TNBC的潜在特异性药物靶点。所提出的策略不仅有助于确定BC,也有助于确定其他癌症的生物标记和治疗靶基因。
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来源期刊
Biotechnology and Bioprocess Engineering
Biotechnology and Bioprocess Engineering 工程技术-生物工程与应用微生物
CiteScore
5.00
自引率
12.50%
发文量
79
审稿时长
3 months
期刊介绍: Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.
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