文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

基因组和表达谱分析揭示早期乳腺癌骨髓中播散肿瘤细胞的分子异质性。

Genomic and expression profiling reveal molecular heterogeneity of disseminated tumor cells in bone marrow of early breast cancer.

作者信息

Magbanua Mark Jesus M, Rugo Hope S, Hauranieh Louai, Roy Ritu, Scott Janet H, Lee Jen Chieh, Hsiao Feng, Sosa Eduardo V, Van't Veer Laura, Esserman Laura J, Park John W

机构信息

1Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA USA.

2Helen Diller Family Comprehensive Cancer Center and Computational Biology and Informatics, University of California, San Francisco, San Francisco, CA USA.

出版信息

NPJ Breast Cancer. 2018 Sep 5;4:31. doi: 10.1038/s41523-018-0083-5. eCollection 2018.


DOI:10.1038/s41523-018-0083-5
PMID:30211312
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6125436/
Abstract

Detection of disseminated tumor cells (DTCs) in bone marrow is an established negative prognostic factor. We isolated small pools of (~20) EPCAM-positive DTCs from early breast cancer patients for genomic profiling. Genome-wide copy number profiles of DTC pools ( = 45) appeared less aberrant than the corresponding primary tumors (PT,  = 16). mutations were detected in 26% of DTC pools ( = 53), none of them were shared with matched PTs. Expression profiling of DTC pools ( = 30) confirmed the upregulation of expression and certain oncogenes (e.g., and ), as well as the absence of hematopoietic features. Two expression subtypes were observed: (1) luminal with dual epithelial-mesenchymal properties (high and expression), and (2) basal-like with proliferative/stem cell-like phenotype (low and high expression). We observed high discordance between (40%) and (43%) expression in DTC pools vs. the clinical ER and HER2 status of the corresponding primary tumors, suggesting plasticity of biomarker status during dissemination to the bone marrow. Comparison of expression profiles of DTC pools with available data from circulating tumor cells (CTCs) of metastatic breast cancer patients revealed gene expression signatures in DTCs that were unique from those of CTCs. For example, , , and were upregulated in DTC pools relative to CTCs. Taken together, analysis of pooled DTCs revealed molecular heterogeneity, possible genetic divergence from corresponding primary tumor, and two distinct subpopulations. Validation in larger cohorts is needed to confirm the presence of these molecular subtypes and to evaluate their biological and clinical significance.

摘要

骨髓中播散性肿瘤细胞(DTCs)的检测是一个已确定的负面预后因素。我们从早期乳腺癌患者中分离出少量(约20个)EPCAM阳性DTCs用于基因组分析。DTC样本库(n = 45)的全基因组拷贝数图谱显示,其异常程度低于相应的原发性肿瘤(PT,n = 16)。在26%的DTC样本库(n = 53)中检测到突变,其中没有一个与匹配的原发性肿瘤共享。DTC样本库(n = 30)的表达谱分析证实了某些基因和癌基因(如 和 )的上调,以及造血特征的缺失。观察到两种表达亚型:(1)具有双重上皮-间质特性的管腔型(高 和 表达),以及(2)具有增殖/干细胞样表型的基底样型(低 和高 表达)。我们观察到DTC样本库中的 (40%)和 (43%)表达与相应原发性肿瘤的临床ER和HER2状态之间存在高度不一致,这表明在向骨髓播散过程中生物标志物状态具有可塑性。将DTC样本库的表达谱与转移性乳腺癌患者循环肿瘤细胞(CTC)的现有数据进行比较,发现DTC中的基因表达特征与CTC不同。例如,相对于CTC, 、 和 在DTC样本库中上调。综上所述,对合并的DTCs分析揭示了分子异质性、与相应原发性肿瘤可能的基因差异以及两个不同的亚群。需要在更大的队列中进行验证,以确认这些分子亚型的存在,并评估它们的生物学和临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/86ece9d0b398/41523_2018_83_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/80f8af8d6dff/41523_2018_83_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/fd72d3934f91/41523_2018_83_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/3544f7069507/41523_2018_83_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/ed46dca2d85e/41523_2018_83_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/00cbb5c9a6fe/41523_2018_83_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/86ece9d0b398/41523_2018_83_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/80f8af8d6dff/41523_2018_83_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/fd72d3934f91/41523_2018_83_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/3544f7069507/41523_2018_83_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/ed46dca2d85e/41523_2018_83_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/00cbb5c9a6fe/41523_2018_83_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8deb/6125436/86ece9d0b398/41523_2018_83_Fig6_HTML.jpg

相似文献

[1]
Genomic and expression profiling reveal molecular heterogeneity of disseminated tumor cells in bone marrow of early breast cancer.

NPJ Breast Cancer. 2018-9-5

[2]
Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow.

BMC Cancer. 2014-6-19

[3]
Predictive factors for the presence of tumor cells in bone marrow and peripheral blood in breast cancer patients.

Neoplasma. 2015

[4]
Estrogen Receptor and HER2 Status on Disseminated Tumor Cells and Primary Tumor in Patients with Early Breast Cancer.

Transl Oncol. 2015-12

[5]
Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts.

Clin Exp Metastasis. 2019-6-12

[6]
Detection of minimal residual disease in blood and bone marrow in early stage breast cancer.

Cancer. 2010-7-15

[7]
Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis.

Breast Cancer Res. 2015-1-9

[8]
Integrated EpCAM-independent subtraction enrichment and iFISH strategies to detect and classify disseminated and circulating tumors cells.

Clin Transl Med. 2015-12

[9]
Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors.

Cancers (Basel). 2023-1-17

[10]
Pro-metastatic and mesenchymal gene expression signatures characterize circulating tumor cells of neuroblastoma patients with bone marrow metastases and relapse.

Front Oncol. 2022-9-13

引用本文的文献

[1]
Antitumor CD4+ T Helper 1 Cells Target and Control the Outgrowth of Disseminated Cancer Cells.

Cancer Immunol Res. 2025-5-2

[2]
Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells.

Diagnostics (Basel). 2024-9-29

[3]
Role of Caveolae family-related proteins in the development of breast cancer.

Front Mol Biosci. 2023-9-27

[4]
Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis.

Cells. 2023-6-6

[5]
Awakening of Dormant Breast Cancer Cells in the Bone Marrow.

Cancers (Basel). 2023-6-1

[6]
Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors.

Cancers (Basel). 2023-1-17

[7]
Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

Breast Cancer Res Treat. 2023-4

[8]
Liquid biopsy for monitoring of tumor dormancy and early detection of disease recurrence in solid tumors.

Cancer Metastasis Rev. 2023-3

[9]
Evaluation of disseminated tumor cells and circulating tumor cells in patients with breast cancer receiving adjuvant zoledronic acid.

NPJ Breast Cancer. 2021-9-6

[10]
Harnessing the power of antibodies to fight bone metastasis.

Sci Adv. 2021-6

本文引用的文献

[1]
Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).

Clin Cancer Res. 2018-1-8

[2]
Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer.

Cancer Res. 2017-8-15

[3]
Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

Br J Cancer. 2017-8-22

[4]
MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis.

Cell Death Dis. 2017-6-22

[5]
Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.

Genome Biol. 2016-12-9

[6]
COSMIC: somatic cancer genetics at high-resolution.

Nucleic Acids Res. 2017-1-4

[7]
Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone.

J Biol Chem. 2016-9-9

[8]
TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis.

Oncotarget. 2016-7-5

[9]
Overexpression of SPARC correlates with poor prognosis in patients with cervical carcinoma and regulates cancer cell epithelial-mesenchymal transition.

Oncol Lett. 2016-5

[10]
Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients.

Oncology. 2016

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索