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单细胞组学:胰腺癌早期检测的新视角?

Single-cell omics: a new perspective for early detection of pancreatic cancer?

机构信息

Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.

出版信息

Eur J Cancer. 2023 Sep;190:112940. doi: 10.1016/j.ejca.2023.112940. Epub 2023 Jun 16.

DOI:10.1016/j.ejca.2023.112940
PMID:37413845
Abstract

Pancreatic cancer is one of the most lethal cancers, mostly due to late diagnosis and limited treatment options. Early detection of pancreatic cancer in high-risk populations bears the potential to greatly improve outcomes, but current screening approaches remain of limited value despite recent technological advances. This review explores the possible advantages of liquid biopsies for this application, particularly focusing on circulating tumour cells (CTCs) and their subsequent single-cell omics analysis. Originating from both primary and metastatic tumour sites, CTCs provide important information for diagnosis, prognosis and tailoring of treatment strategies. Notably, CTCs have even been detected in the blood of subjects with pancreatic precursor lesions, suggesting their suitability as a non-invasive tool for the early detection of malignant transformation in the pancreas. As intact cells, CTCs offer comprehensive genomic, transcriptomic, epigenetic and proteomic information that can be explored using rapidly developing techniques for analysing individual cells at the molecular level. Studying CTCs during serial sampling and at single-cell resolution will help to dissect tumour heterogeneity for individual patients and among different patients, providing new insights into cancer evolution during disease progression and in response to treatment. Using CTCs for non-invasive tracking of cancer features, including stemness, metastatic potential and expression of immune targets, provides important and readily accessible molecular insights. Finally, the emerging technology of ex vivo culturing of CTCs could create new opportunities to study the functionality of individual cancers at any stage and develop personalised and more effective treatment approaches for this lethal disease.

摘要

胰腺癌是最致命的癌症之一,主要原因是诊断较晚和治疗选择有限。在高危人群中早期发现胰腺癌有可能极大地改善预后,但尽管最近取得了技术进步,目前的筛查方法仍然价值有限。本综述探讨了液体活检在这一应用中的可能优势,特别是重点关注循环肿瘤细胞(CTC)及其随后的单细胞组学分析。CTC 源自原发性和转移性肿瘤部位,为诊断、预后和治疗策略的制定提供了重要信息。值得注意的是,在有胰腺前驱病变的受试者的血液中甚至已经检测到了 CTC,这表明它们适合作为一种非侵入性工具,用于早期发现胰腺中的恶性转化。作为完整的细胞,CTC 提供了全面的基因组、转录组、表观基因组和蛋白质组信息,可以使用快速发展的技术在分子水平上分析单个细胞来进行探索。在连续采样和单细胞分辨率下研究 CTC 有助于剖析个体患者和不同患者之间的肿瘤异质性,为疾病进展过程中的癌症演变以及对治疗的反应提供新的见解。使用 CTC 进行非侵入性跟踪癌症特征,包括干性、转移潜力和免疫靶标的表达,提供了重要且易于获取的分子见解。最后,CTC 的体外培养新兴技术可能为在任何阶段研究个体癌症的功能并为这种致命疾病开发个性化和更有效的治疗方法创造新的机会。

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