Multiplex imaging of breast cancer lymph node metastases identifies prognostic single-cell populations independent of clinical classifiers.
Multiplex imaging of breast cancer lymph node metastases identifies prognostic single-cell populations independent of clinical classifiers.
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DOI：
10.1016/j.xcrm.2023.100977
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发表时间：
2023-03-21
影响因子：
14.3
通讯作者：
Bodenmiller, Bernd
中科院分区：
文献类型：
--
作者：
Fischer, Jana Raja;Jackson, Hartland Warren;de Souza, Natalie;Varga, Zsuzsanna;Schraml, Peter;Moch, Holger;Bodenmiller, Bernd
虽然乳腺癌的死亡率主要是由转移引起的，但临床决策是基于对原发肿瘤和淋巴结受累的分析，而不是基于播散细胞的表型。在这里，我们使用多重成像质量细胞术比较205例原发性乳腺肿瘤和匹配的淋巴结转移的单细胞表型。我们观察到广泛的原发和转移部位之间的表型变异性和播散细胞表型经常偏离临床疾病亚型。我们确定了与患者生存相关的播散性肿瘤细胞的单细胞表型和空间组织，以及原发性肿瘤中高风险表型的较弱生存相关性。我们发现，p53和GATA 3在淋巴结转移提供了超出临床分类的预后信息，可以用标准方法测量。播散性肿瘤细胞的分子特征是乳腺癌临床应用预后信息的一个未开发的来源。肿瘤细胞表型在原发性乳腺肿瘤和匹配的淋巴结转移中不同。确定了高风险和低风险的播散细胞表型和预后标志物。肿瘤细胞表型异质性和空间混合与良好的预后相关。使用多重成像质谱细胞术分析具有匹配的原发肿瘤和淋巴结转移的乳腺癌患者队列中的单个肿瘤细胞表型。他们报告了这些组织部位之间的高表型变异性，并描述了与患者预后相关的播散细胞表型和空间组织。
Although breast cancer mortality is largely caused by metastasis, clinical decisions are based on analysis of the primary tumor and on lymph node involvement but not on the phenotype of disseminated cells. Here, we use multiplex imaging mass cytometry to compare single-cell phenotypes of primary breast tumors and matched lymph node metastases in 205 patients. We observe extensive phenotypic variability between primary and metastatic sites and that disseminated cell phenotypes frequently deviate from the clinical disease subtype. We identify single-cell phenotypes and spatial organizations of disseminated tumor cells that are associated with patient survival and a weaker survival association for high-risk phenotypes in the primary tumor. We show that p53 and GATA3 in lymph node metastases provide prognostic information beyond clinical classifiers and can be measured with standard methods. Molecular characterization of disseminated tumor cells is an untapped source of clinically applicable prognostic information for breast cancer. Tumor cell phenotypes differ in primary breast tumors and matched lymph node metastases High- and low-risk disseminated cell phenotypes and prognostic markers are identified Tumor cell phenotypic heterogeneity and spatial mixing is associated with good outcome Disseminated tumor cell phenotypes are an untapped source of clinical information Fischer et al. use multiplex imaging mass cytometry to analyze single tumor cell phenotypes in a breast cancer patient cohort with matched primary tumors and lymph node metastases. They report high phenotypic variability between these tissue sites and describe disseminated cell phenotypes and spatial organization associated with patient prognosis.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
--
作者：
Stefanovic S;Wirtz R;Deutsch TM;Hartkopf A;Sinn P;Varga Z;Sobottka B;Sotiris L;Taran FA;Domschke C;Hennigs A;Brucker SY;Sohn C;Schuetz F;Schneeweiss A;Wallwiener M
通讯作者：
Wallwiener M
影响因子：
22.7
作者：
Ali, H. Raza;Jackson, Hartland W.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
通讯作者：
Chen J