Multiplexed digital spatial profiling of invasive breast tumors from Black and White women.

Multiplexed digital spatial profiling of invasive breast tumors from Black and White women.
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DOI:
10.1002/1878-0261.13017
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发表时间:
2022-01
期刊:
影响因子:
6.6
通讯作者:
Yao S
Yao S
中科院分区:
医学2区
文献类型:
--
作者:
Omilian AR;Sheng H;Hong CC;Bandera EV;Khoury T;Ambrosone CB;Yao S

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NanoString GeoMx数字空间分析是一种新的多路复用平台,以空间分辨的方式定量肿瘤和免疫相关蛋白的丰度。我们进行了DSP,以同时评估由泛细胞角蛋白表达定义的空间分辨组织区室中的52种分析物。我们比较了94例非洲裔美国人/黑人和65例欧洲裔美国人/白色病例的蛋白质靶点、肿瘤和间质组织区室、雌激素受体α(ER)阳性和ER阴性病例,并探索了潜在的生存生物标志物。在具有稳健分析信号的33种分析物中,结果具有高度可重复性。对于标记物的子集,DSP分析物和传统免疫组织化学评分之间的相关性分析显示两个平台之间存在中度至非常强的相关性。同样,DSP分析物和基因表达评分对于25个标记物中的21个是一致的,两个数据集之间存在重叠。几种分析物因ER状态而异,在调查的25种免疫标志物中,14种与ER表达呈显著负相关。B7同源物3(B7-H3;由CD 276编码)是唯一一种显示出种族显著差异的分析物,在黑人女性的肿瘤和间质区室中均较低。与生存相关的DSP标志物包括CD 8、CD 25、CD 56、CD 127、EpCAM、ER、Ki-67和STING。我们得出结论,DSP是一种同时筛选肿瘤和免疫相关标志物的有效工具,其结果与已建立的免疫分析方法一致。DSP免疫分析物与ER表达呈负相关,这与先前大量工作一致,这些工作记录了ER阴性乳腺癌中较高的免疫浸润。这项技术显示,与白色女性相比,黑人女性乳腺癌中B7‐H3蛋白的评分显著较低,这是一个有趣的发现,需要在独立和种族多样的女性人群中复制。我们评估了NanoString GeoMx数字空间分析平台在患有浸润性乳腺癌的黑人和白色女性人群中的高度多重免疫分析。使用DSP进行发现和常规免疫组织化学和基因表达数据进行验证,我们发现DSP技术是有效的,可重复的,并产生与已建立的免疫分析测定一致的结果。
The NanoString GeoMx digital spatial profiling is a new multiplexed platform that quantifies the abundance of tumor‐ and immune‐related proteins in a spatially resolved manner. We performed DSP for the simultaneous assessment of 52 analytes within spatially resolved tissue compartments defined by pan‐cytokeratin expression. We compared protein targets between 94 African American/Black and 65 European American/White cases, tumor and stromal tissue compartments, estrogen receptor alpha (ER)‐positive and ER‐negative cases, and explored potential biomarkers of survival. Of 33 analytes with robust signal for analysis, results were highly replicable. For a subset of markers, correlative analyses between DSP analytes and traditional immunohistochemistry scores revealed moderate to very strong associations between the two platforms. Similarly, DSP analytes and gene expression scores were concordant for 21 of 25 markers with overlap between the two datasets. Several analytes varied by ER status, and across the 25 immune markers surveyed, 14 had a significant inverse association with ER expression. B7 homolog 3 (B7‐H3; encoded by CD276) was the only analyte to show a significant difference by race, being lower in both the tumor and stromal compartments in Black women. DSP markers that were associated with survival included CD8, CD25, CD56, CD127, EpCAM, ER, Ki‐67, and STING. We conclude that DSP is an efficient tool for screening tumor‐ and immune‐related markers in a simultaneous fashion and yields results that are concordant with established immune profiling assays. DSP immune analytes were inversely associated with ER expression, in agreement with a substantial body of previous work that documents higher immune infiltration in ER‐negative breast cancers. This technology revealed that scores of the B7‐H3 protein were significantly lower in breast cancers from Black women compared with White women, an intriguing finding that requires replication in independent and racially diverse female populations. We evaluated the NanoString GeoMx digital spatial profiling platform for highly multiplexed immune profiling in a population of Black and White women with invasive breast cancer. Using DSP for discovery and conventional immunohistochemistry and gene expression data for validation, we found the DSP technology to be efficient, reproducible, and to yield results that are concordant with established immune profiling assays.
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发表时间: 2016-09-15
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