Deciphering Breast Cancer Metastasis Cascade: A Systems Biology Approach Integrating Transcriptome and Interactome Insights for Target Discovery.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-03-01 Epub Date: 2024-03-14 DOI:10.1089/omi.2023.0285
Bikashita Kalita, Mohane Selvaraj Coumar
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Abstract

Breast cancer is the lead cause of cancer-related deaths among women globally. Breast cancer metastasis is a complex and still inadequately understood process and a key dimension of mortality attendant to breast cancer. This study reports dysregulated genes across metastatic stages and tissues, shedding light on their molecular interplay in disease pathogenesis and new possibilities for drug discovery. Comprehensive analyses of gene expression data from primary breast tumor, circulating tumor cells, and distant metastatic sites in the brain, lung, liver, and bone were conducted. Genes dysregulated across multiple stages and tissues were identified as metastatic cascade genes, and are further classified based on functional associations with metastasis-related mechanisms. Their interactions with HUB genes in interactome networks were scrutinized, followed by pathway enrichment analysis. Validation for their potential as targets included assessments for survival, druggability, prognostic marker status, secretome annotation, protein expression, and cell type marker association. Results displayed critical genes in the metastatic cascade and those specific to metastatic sites, revealing the involvement of the collagen degradation and assembly of collagen fibrils and other multimeric structure pathways in driving metastasis. Notably, pivotal cascade genes FABP4, CXCL12, APOD, and IGF1 emerged with high metastatic potential, linked to significant druggability and survival scores, establishing them as potential molecular targets. The significance of this research lies in its potential to uncover novel biomarkers for early detection, therapeutic targets, and a deeper understanding of the molecular mechanisms underpinning the metastatic cascade in breast cancer, and with an eye to precision/personalized medicine.

解密乳腺癌转移级联:整合转录组和相互作用组洞察力以发现目标的系统生物学方法。
乳腺癌是全球妇女因癌症死亡的主要原因。乳腺癌转移是一个复杂的过程,人们对它的了解还很不够,这也是导致乳腺癌患者死亡的一个关键因素。本研究报告了各转移阶段和组织中的失调基因,揭示了它们在疾病发病机制中的分子相互作用,为药物发现提供了新的可能性。研究人员对原发性乳腺肿瘤、循环肿瘤细胞以及脑、肺、肝和骨等远处转移部位的基因表达数据进行了全面分析。在多个阶段和组织中表达失调的基因被鉴定为转移级联基因,并根据其与转移相关机制的功能关联进行了进一步分类。研究人员仔细研究了这些基因与相互作用组网络中的 HUB 基因之间的相互作用,然后进行了通路富集分析。对这些基因作为靶点的潜力进行了验证,包括生存率、可药用性、预后标志物状态、分泌组注释、蛋白质表达和细胞类型标志物关联的评估。结果显示了转移级联中的关键基因和转移部位的特异性基因,揭示了胶原降解和胶原纤维组装以及其他多聚体结构通路参与驱动转移。值得注意的是,关键级联基因 FABP4、CXCL12、APOD 和 IGF1 具有较高的转移潜能,与显著的可药性和存活率评分相关,从而将它们确立为潜在的分子靶点。这项研究的意义在于它有可能发现用于早期检测的新型生物标记物、治疗靶点,并加深对支撑乳腺癌转移级联的分子机制的理解,同时着眼于精准/个性化医疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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