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基于微流控的癌症液体活检技术:揭示水平基因转移(HGT)物质的作用。

Microfluidic-based technologies in cancer liquid biopsy: Unveiling the role of horizontal gene transfer (HGT) materials.

机构信息

Applied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90024, United States.

出版信息

Environ Res. 2023 Dec 1;238(Pt 1):117083. doi: 10.1016/j.envres.2023.117083. Epub 2023 Sep 9.

DOI:10.1016/j.envres.2023.117083
PMID:37690629
Abstract

Liquid biopsy includes the isolating and analysis of non-solid biological samples enables us to find new ways for molecular profiling, prognostic assessment, and better therapeutic decision-making in cancer patients. Despite the conventional theory of tumor development, a non-vertical transmission of DNA has been reported among cancer cells and between cancer and normal cells. The phenomenon referred to as horizontal gene transfer (HGT) has the ability to amplify the advancement of tumors by disseminating genes that encode molecules conferring benefits to the survival or metastasis of cancer cells. Currently, common liquid biopsy approaches include the analysis of extracellular vesicles (EVs) and tumor-free DNA (tfDNA) derived from primary tumors and their metastatic sites, which are well-known HGT mediators in cancer cells. Current technological and molecular advances expedited the high-throughput and high-sensitive HGT materials analyses by using new technologies, such as microfluidics in liquid biopsies. This review delves into the convergence of microfluidic-based technologies and the investigation of Horizontal Gene Transfer (HGT) materials in cancer liquid biopsy. The integration of microfluidics offers unprecedented advantages such as high sensitivity, rapid analysis, and the ability to analyze rare cell populations. These attributes are instrumental in detecting and characterizing CTCs, circulating nucleic acids, and EVs, which are carriers of genetic cargo that could potentially undergo HGT. The phenomenon of HGT in cancer has raised intriguing questions about its role in driving genomic diversity and acquired drug resistance. By leveraging microfluidic platforms, researchers have been able to capture and analyze individual cells or genetic material with enhanced precision, shedding light on the potential transfer of genetic material between cancer cells and surrounding stromal cells. Furthermore, the application of microfluidics in single-cell sequencing has enabled the elucidation of the genetic changes associated with HGT events, providing insights into the evolution of tumor genomes. This review also discusses the challenges and opportunities in studying HGT materials using microfluidic-based technologies. In conclusion, microfluidic-based technologies have significantly advanced the field of cancer liquid biopsy, enabling the sensitive and accurate detection of HGT materials. As the understanding of HGT's role in tumor evolution and therapy resistance continues to evolve, the synergistic integration of microfluidics and HGT research promises to provide valuable insights into cancer biology, with potential implications for precision oncology and therapeutic strategies.

摘要

液体活检包括非固态生物样本的分离和分析,使我们能够找到新的方法来对癌症患者进行分子谱分析、预后评估和更好的治疗决策。尽管存在肿瘤发生的传统理论,但已经有报道称癌细胞之间以及癌细胞和正常细胞之间存在非垂直传递的 DNA。这种被称为水平基因转移(HGT)的现象具有通过传播赋予癌细胞生存或转移优势的分子来放大肿瘤进展的能力。目前,常见的液体活检方法包括分析源自原发性肿瘤及其转移部位的细胞外囊泡(EVs)和无肿瘤游离 DNA(tfDNA),它们是癌细胞中众所周知的 HGT 介质。当前的技术和分子进展通过使用新技术(如液体活检中的微流控技术)加速了高通量和高灵敏度的 HGT 材料分析。本综述深入探讨了基于微流控的技术与癌症液体活检中水平基因转移(HGT)材料的研究融合。微流控技术的集成提供了前所未有的优势,例如高灵敏度、快速分析以及分析稀有细胞群体的能力。这些特性对于检测和表征循环肿瘤细胞(CTC)、循环核酸和 EV 非常重要,它们是可能发生 HGT 的遗传物质的载体。癌症中的 HGT 现象引发了关于其在驱动基因组多样性和获得性药物耐药性中的作用的有趣问题。通过利用微流控平台,研究人员能够以更高的精度捕获和分析单个细胞或遗传物质,揭示了癌细胞与周围基质细胞之间遗传物质转移的潜力。此外,微流控在单细胞测序中的应用使阐明与 HGT 事件相关的遗传变化成为可能,为肿瘤基因组的进化提供了见解。本综述还讨论了使用基于微流控的技术研究 HGT 材料的挑战和机遇。总之,基于微流控的技术显著推进了癌症液体活检领域,实现了 HGT 材料的敏感和准确检测。随着对 HGT 在肿瘤进化和治疗耐药性中的作用的理解不断发展,微流控与 HGT 研究的协同整合有望为癌症生物学提供有价值的见解,并可能对精准肿瘤学和治疗策略产生影响。

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