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癌症早期生物学研究的新策略
Emerging strategies to investigate the biology of early cancer
Nature 等信源发布 2024-10-21 02:07
可切换为仅中文
AbstractEarly detection and intervention of cancer or precancerous lesions hold great promise to improve patient survival. However, the processes of cancer initiation and the normal–precancer–cancer progression within a non-cancerous tissue context remain poorly understood. This is, in part, due to the scarcity of early-stage clinical samples or suitable models to study early cancer.
摘要癌症或癌前病变的早期发现和干预有望提高患者的生存率。然而，在非癌组织背景下，癌症的发生过程和正常的癌前癌症进展仍然知之甚少。这部分是由于缺乏早期临床样本或研究早期癌症的合适模型。
In this Review, we introduce clinical samples and model systems, such as autochthonous mice and organoid-derived or stem cell-derived models that allow longitudinal analysis of early cancer development. We also present the emerging techniques and computational tools that enhance our understanding of cancer initiation and early progression, including direct imaging, lineage tracing, single-cell and spatial multi-omics, and artificial intelligence models.
在这篇综述中，我们介绍了临床样本和模型系统，例如原生小鼠和类器官衍生或干细胞衍生的模型，这些模型可以对早期癌症发展进行纵向分析。我们还介绍了新兴技术和计算工具，以增强我们对癌症发生和早期进展的理解，包括直接成像，谱系追踪，单细胞和空间多组学以及人工智能模型。
Together, these models and techniques facilitate a more comprehensive understanding of the poorly characterized early malignant transformation cascade, holding great potential to unveil key drivers and early biomarkers for cancer development. Finally, we discuss how these new insights can potentially be translated into mechanism-based strategies for early cancer detection and prevention..
总之，这些模型和技术有助于更全面地了解表征不佳的早期恶性转化级联反应，具有揭示癌症发展的关键驱动因素和早期生物标志物的巨大潜力。最后，我们讨论如何将这些新见解转化为基于机制的早期癌症检测和预防策略。。
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Access Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription24,99 € / 30 dayscancel any timeLearn moreSubscription info for Chinese customersWe have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.Go to naturechina.comBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkout.
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Fig. 1: The multistage malignant transformation cascade of normal cells.Fig. 2: Clinical samples and preclinical models for early cancer.
图1：正常细胞的多阶段恶性转化级联。图2：早期癌症的临床样本和临床前模型。
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Download referencesAcknowledgementsY.W. gratefully acknowledges funding from the National Natural Science Foundation of China (82425037, 92359303, 82273117), the National Key R&D Program of China, Stem Cell and Translational Research (2022YFA1105200), Sichuan Science and Technology Program (2023ZYD0128, 2024NSFSC0059) and West China Hospital (ZYYC23023).
下载referencesAcknowledgementsY。W、 感谢国家自然科学基金（824250379235930382273117）、国家重点研发计划、干细胞与转化研究（2022YFA1105200）、四川省科学技术计划（2023ZYD01282024NSFSC0059）和华西医院（ZYC23023）的资助。
R.Z. thanks the National Natural Science Foundation of China (82303975), the China Postdoctoral Science Foundation (2022TQ0226 and 2023M742492) and West China Hospital (2023HXBH100). After completing the final manuscript, the authors utilized ChatGPT (OpenAI, https://chat.openai.com/) to proofread the final draft.Author informationAuthors and AffiliationsDepartment of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaRan Zhou, Xiwen Tang & Yuan WangAuthorsRan ZhouView author publicationsYou can also search for this author in.
R、 Z.感谢国家自然科学基金（82303975），中国博士后科学基金（2022TQ0226和2023M742492）和华西医院（2023HXBH100）。，https://chat.openai.com/)校对定稿。作者信息作者和附属机构四川大学华西医院生物治疗与癌症中心国家重点实验室神经外科，中国成都，周冉，汤锡文和王元作者周冉观点作者出版物您也可以在中搜索这位作者。
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PubMed Google ScholarContributionsR.Z. and X.T. researched data for the article. R.Z. and Y.W. wrote the article. All authors reviewed or edited the manuscript before submission.Corresponding authorCorrespondence to
PubMed谷歌学术贡献。Z、 和X.T.为本文研究了数据。R、 。所有作者在提交前都审阅或编辑了手稿。对应作者对应
Yuan Wang.Ethics declarations
王元。道德宣言
Competing interests
相互竞争的利益
The authors declare no competing interests.
作者声明没有利益冲突。
Peer review
同行评审
Peer review information
同行评审信息
Nature Reviews Cancer thanks Toshiro Sato, Rebecca Fitzgerald and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
《自然评论癌症》感谢佐藤敏弘、丽贝卡·菲茨杰拉德和另一位匿名审稿人对这项工作的同行评议做出的贡献。
Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Related linksATCC: https://www.atcc.orginferCNV: https://github.com/broadinstitute/infercnvPreCancer Atlas: https://prevention.cancer.gov/major-programs/pre-cancer-atlas-pcasiCNV: https://github.com/aerickso/SpatialInferCNVGlossaryAcinar-to-ductal metaplasia.
。相关链接ATCC：https://www.atcc.orginferCNV:（笑声）https://github.com/broadinstitute/infercnvPreCancer地图集：https://prevention.cancer.gov/major-programs/pre-cancer-atlas-pcasiCNV:（笑声）https://github.com/aerickso/SpatialInferCNVGlossaryAcinar-to-ductal化生。
The transformation of pancreatic acinar cells into duct-like cells in response to pancreatic injury or chronic stress that is considered a precursor to pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma.
胰腺腺泡细胞向导管样细胞的转化，以响应胰腺损伤或慢性应激，这被认为是胰腺上皮内瘤变和胰腺导管腺癌的前兆。
Actinic keratosis
光化性角化病
A rough, dry and scaly patch or plaque on the skin, considered a precursor to squamous cell carcinoma of the skin, that is associated with risk factors such as sun exposure, human papillomavirus, fair skin, immunosuppressive therapy and age.
皮肤上粗糙、干燥、鳞状的斑块或斑块，被认为是皮肤鳞状细胞癌的前兆，与阳光照射、人乳头瘤病毒、皮肤白皙、免疫抑制治疗和年龄等危险因素有关。
Adenomas
腺瘤
Benign tumours originating from glandular epithelial tissue in various organs, including the colon, pituitary gland, thyroid, adrenal glands and liver.
良性肿瘤起源于各种器官的腺上皮组织，包括结肠、垂体、甲状腺、肾上腺和肝脏。
Assay for transposase-accessible chromatin with sequencing
转座酶可及染色质的测序分析
(ATAC-seq). A widely utilized method to assess the accessibility of chromatin within cells.
。一种广泛使用的评估细胞内染色质可及性的方法。
Assembloids
集合体
3D in vitro tissue models that integrates multiple organoid types or cell lineages to replicate the complex interactions and architecture of tissues.
3D体外组织模型，整合了多种类器官类型或细胞谱系，以复制组织的复杂相互作用和结构。
Atypical adenomatous hyperplasia
A term predominantly used in lung pathology to describe precursor lesions of lung adenocarcinoma; however, it can occasionally be applied to other organs to denote abnormal, precancerous growth patterns in glandular tissues.
一个主要用于肺部病理学的术语，用于描述肺腺癌的前体病变；然而，它偶尔也可以应用于其他器官，以表示腺组织中异常的癌前生长模式。
Atypical endometrial hyperplasia
不典型子宫内膜增生
Also known as endometrial intraepithelial neoplasia. A precancerous condition characterized by the abnormal proliferation of the cells lining the endometrium with atypical cellular features.
也称为子宫内膜上皮内瘤变。子宫内膜癌前病变，其特征是子宫内膜衬里细胞异常增殖，具有非典型细胞特征。
Autochthonous mouse models
本地鼠标模型
Mouse models in which cancer arises naturally within the mouse, typically induced through genetic modifications or exposure to carcinogens.
小鼠模型，其中癌症在小鼠体内自然产生，通常通过基因修饰或暴露于致癌物诱导。
Barrett’s oesophagus
Barrett’s oesophagus precedes the onset of oesophageal adenocarcinoma and involves a metaplastic change in the mucosal cells within the lower part of the oesophagus, a response to damage from gastro-oesophageal reflux.
Barrett食管先于食管腺癌发作，并涉及食管下部粘膜细胞的化生变化，这是对胃食管反流损伤的反应。
Chronic atrophic gastritis
慢性萎缩性胃炎
A long-term condition characterized by the chronic inflammation of the stomach lining, leading to the gradual loss of gastric glandular cells, resulting in stomach lining atrophy that can be accompanied by changes in the structure of the stomach lining, potentially leading to intestinal metaplasia and an increased risk of gastric cancer..
一种以胃粘膜慢性炎症为特征的长期疾病，导致胃腺细胞逐渐丧失，导致胃粘膜萎缩，并伴有胃粘膜结构的改变，可能导致肠化生和胃癌风险增加。。
Club cells
俱乐部细胞
A type of non-ciliated epithelial cells located in the bronchioles of the lungs, which is essential for maintaining the health and function of the respiratory epithelium.
位于肺细支气管中的一种非纤毛上皮细胞，对维持呼吸道上皮的健康和功能至关重要。
Dysplasia
发育不良
An abnormal growth or development of cells within a tissue, exhibiting irregularities in size, shape, organization and cellular structure, with severity ranging from mild to severe, with high-grade dysplasia carrying a risk of progressing to cancer.
组织内细胞的异常生长或发育，在大小、形状、组织和细胞结构上表现出不规则性，严重程度从轻度到重度不等，高度不典型增生有发展为癌症的风险。
Extrachromosomal DNA
染色体外DNA
(ecDNA). Any DNA that is often larger than 1 Mb and is located outside the chromosomes.
（ecDNA）。任何通常大于1 Mb且位于染色体之外的DNA。
Familial adenomatous polyposis
家族性腺瘤性息肉病
A type of syndromic polyp associated with genetic syndromes that predisposes individuals to the development of hundreds to thousands of adenomatous polyps in the colon and rectum, which almost inevitably progresses to colorectal cancer.
一种与遗传综合征相关的综合征性息肉，易使个体在结肠和直肠中发展成百上千的腺瘤性息肉，几乎不可避免地发展为结直肠癌。
Field cancerization
现场癌变
A process through which a broad region of cells within a tissue or organ undergoes genetic and epigenetic alterations, thereby predisposing the entire field to an elevated risk of developing cancer.
一种过程，通过该过程，组织或器官内的广泛细胞区域发生遗传和表观遗传改变，从而使整个领域易患癌症的风险升高。
Hyperplasia
增生
Hyperplasia is a reversible process that involves an increase in the number of cells in a tissue, which can occur owing to physiological or pathological triggers.
增生是一个可逆的过程，涉及组织中细胞数量的增加，这可能是由于生理或病理触发而发生的。
Intravital microscopy
活体显微镜检查
(IVM). A technique to visualize cells within a living organism using fluorescent markers or dyes that encompasses various methods, including confocal microscopy, two-photon microscopy and multiphoton microscopy.
（IVM）。一种使用荧光标记或染料可视化生物体内细胞的技术，包括各种方法，包括共聚焦显微镜、双光子显微镜和多光子显微镜。
Large language models
Advanced machine learning algorithms designed to grasp the intricacies, patterns and subtleties of human language by analysing data sets containing billions of words.
先进的机器学习算法，旨在通过分析包含数十亿个单词的数据集来掌握人类语言的复杂性、模式和微妙之处。
Leukoplakia
白斑
White patches or plaques in the oral or genital regions with the potential to progress to squamous cell carcinoma, which is associated with risk factors including tobacco use, alcohol consumption, chronic irritation, viral infections such as HPV, and age and gender.
口腔或生殖器区域的白色斑块或斑块有可能发展为鳞状细胞癌，这与危险因素有关，包括吸烟，饮酒，慢性刺激，HPV等病毒感染以及年龄和性别。
Low-grade intraepithelial neoplasia
低度上皮内瘤变
(LGIN). A precancerous condition characterized by the presence of mildly abnormal epithelial cells confined to the epithelial layer of the oesophagus that has a lower risk of progression to oesophageal cancer than high-grade intraepithelial neoplasia (HGIN).
（LGIN）。一种癌前病变，其特征是存在局限于食管上皮层的轻度异常上皮细胞，其进展为食管癌的风险低于高度上皮内瘤变（HGIN）。
Metaplasia
化生
A reversible process through which one differentiated cell is replaced by another cell type, typically in response to persistent irritation or inflammation.
一种可逆的过程，通过该过程，一种分化的细胞被另一种细胞类型取代，通常是对持续刺激或炎症的反应。
Monoclonal gammopathy of undetermined significance
意义不明的单克隆丙种球蛋白病
A precancerous condition with a modest risk of progression to more severe plasma cell disorders that is characterized by the presence of an abnormal monoclonal protein in the blood, produced by a clone of plasma cells.
一种癌前状态，具有发展为更严重浆细胞疾病的适度风险，其特征是血液中存在由浆细胞克隆产生的异常单克隆蛋白。
Neoplastic polyps
肿瘤性息肉
Polyps with the potential to develop into colorectal cancer that can be classified into adenomatous polyps (including tubular, tubulovillous and villous types) and serrated polyps (including sessile serrated lesions and traditional serrated adenomas).
息肉可能发展为结直肠癌，可分为腺瘤性息肉（包括管状，管状和绒毛型）和锯齿状息肉（包括无柄锯齿状病变和传统锯齿状腺瘤）。
Pancreatic intraepithelial neoplasia
(PanIN). These precursor lesions to pancreatic ductal adenocarcinoma that encompass a spectrum of dysplastic changes are microscopic abnormalities found in the epithelial cells lining the pancreatic ducts and are not detectable through standard imaging techniques.
（帕宁）。这些胰腺导管腺癌的前体病变包括一系列发育异常的变化，是在胰管内衬的上皮细胞中发现的微观异常，通过标准成像技术无法检测到。
Precancerous cells
癌前细胞
Cancer precursor cells that harbour common cancer driver mutations but exist in tissues without clinical evidence of precursor lesions.
癌症前体细胞具有常见的癌症驱动突变，但存在于没有前体病变临床证据的组织中。
Precancerous lesions
癌前病变
Morphological changes in tissues resulting from the acquisition of driver events in individual cells that undergo positive selection and clonal expansion within normal tissues, leading to tissue remodelling.
由于在正常组织内经历阳性选择和克隆扩增的单个细胞中获得驱动事件而导致的组织形态变化，导致组织重塑。
Pulmonary nodules
肺结节
Small, abnormal areas that appear in the lung tissue that can result from infections or scarring, which could potentially lead to lung cancer.
肺组织中出现的小而异常的区域，可能由感染或疤痕引起，可能导致肺癌。
Single-cell multi-omics
单细胞多组学
An advanced genomic technique that enables the simultaneous analysis of multiple types of biological signals such as the genome, transcriptome, proteome and metabolome within the same cell.
一种先进的基因组技术，可以同时分析同一细胞内的多种生物信号，例如基因组，转录组，蛋白质组和代谢组。
Smouldering multiple myeloma
闷烧性多发性骨髓瘤
An asymptomatic, precancerous condition that is considered an intermediate stage between monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma and is characterized by elevated levels of monoclonal protein and a higher percentage of abnormal plasma cells in the bone marrow..
一种无症状的癌前病变，被认为是意义不明的单克隆丙种球蛋白病和症状性多发性骨髓瘤之间的中间阶段，其特征是单克隆蛋白水平升高和骨髓中异常浆细胞百分比较高。。
Spatial transcriptomics
空间转录组学
A method that enables the spatial visualization and quantification of gene expression within a tissue.
一种能够对组织内的基因表达进行空间可视化和定量的方法。
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& Wang, Y. Emerging strategies to investigate the biology of early cancer..
&Wang，Y。研究早期癌症生物学的新兴策略。。
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