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深度学习工具 HEV-finder 自动检测肿瘤引流淋巴结中的血管重构。

Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder.

机构信息

The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

Department of Information Technology, Uppsala University, Uppsala, Sweden.

出版信息

J Pathol. 2022 Sep;258(1):4-11. doi: 10.1002/path.5981. Epub 2022 Jul 12.

DOI:10.1002/path.5981
PMID:35696253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9543492/
Abstract

Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

摘要

血管重构在人类癌症中很常见,具有作为预测疾病进展和肿瘤免疫状态的未来生物标志物的潜力。它还可以影响转移部位,包括肿瘤引流淋巴结 (TDLNs)。已经在几种类型的癌症中观察到 TDLNs 内高内皮静脉 (HEV) 的扩张。我们最近证明,这是一种可以与乳腺癌侵袭性相关的前转移效应。手动评估血管形态变化是一项繁琐且困难的任务,限制了高通量分析。在这里,我们提出了一种用于检测和分类 HEV 扩张的全自动方法。通过使用 12524 个手动分类的 HEV,我们训练了一个深度学习模型,并创建了一个图形用户界面来可视化结果。该工具名为 HEV-finder,可选择性地分析淋巴结特定区域的 HEV 扩张。我们评估了 HEV-finder 与手动注释相比,在不同类型的乳腺癌中检测和分类 HEV 扩张的能力。我们的结果构成了大规模、全自动和用户独立的基于图像的人类病理学中血管重构定量评估的成功范例,并为未来探索 TDLNs 中 HEV 扩张作为生物标志物奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/f324743ca893/PATH-258-4-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/53a17a57ea1c/PATH-258-4-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/a006a40be3ff/PATH-258-4-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/78b3273f9b9a/PATH-258-4-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/f324743ca893/PATH-258-4-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/53a17a57ea1c/PATH-258-4-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/a006a40be3ff/PATH-258-4-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/78b3273f9b9a/PATH-258-4-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd07/9543492/f324743ca893/PATH-258-4-g003.jpg

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本文引用的文献

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Front Mol Biosci. 2021 May 24;8:674558. doi: 10.3389/fmolb.2021.674558. eCollection 2021.
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Deep learning in histopathology: the path to the clinic.深度学习在组织病理学中的应用:通往临床的道路。
Nat Med. 2021 May;27(5):775-784. doi: 10.1038/s41591-021-01343-4. Epub 2021 May 14.
3
Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells.
淋巴结高内皮微静脉的重塑反映了乳腺癌的肿瘤侵袭性,并与血管周围基质细胞的失调有关。
Cancers (Basel). 2021 Jan 8;13(2):211. doi: 10.3390/cancers13020211.
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Biomarker predictors for immunotherapy benefit in breast: beyond PD-L1.乳腺癌免疫治疗获益的生物标志物预测指标:超越程序性死亡受体配体1
Curr Breast Cancer Rep. 2019 Dec;11(4):217-227. doi: 10.1007/s12609-019-00331-5. Epub 2019 Nov 11.
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Clinical Challenges of Immune Checkpoint Inhibitors.免疫检查点抑制剂的临床挑战。
Cancer Cell. 2020 Sep 14;38(3):326-333. doi: 10.1016/j.ccell.2020.07.004. Epub 2020 Aug 3.
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Unlocking the therapeutic potential of primary tumor-draining lymph nodes.解锁原发肿瘤引流淋巴结的治疗潜力。
Cancer Immunol Immunother. 2019 Oct;68(10):1681-1688. doi: 10.1007/s00262-019-02330-y. Epub 2019 Apr 3.
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State-of-the-Art of Profiling Immune Contexture in the Era of Multiplexed Staining and Digital Analysis to Study Paraffin Tumor Tissues.多重染色与数字分析时代石蜡肿瘤组织免疫微环境分析的研究现状
Cancers (Basel). 2019 Feb 20;11(2):247. doi: 10.3390/cancers11020247.
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