Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Mol Oncol. 2022 Jan;16(1):54-68. doi: 10.1002/1878-0261.13017. Epub 2021 Jun 10.
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.
NanoString GeoMx 数字空间分析是一种新的多重平台，可定量分析肿瘤和免疫相关蛋白在空间上的丰度。我们对通过泛细胞角蛋白表达定义的空间分辨组织隔室中 52 种分析物进行了 DSP 分析。我们比较了 94 名非裔美国人/黑人患者和 65 名欧洲裔美国人/白人患者、肿瘤和基质组织隔室、雌激素受体α（ER）阳性和 ER 阴性病例之间的蛋白靶标，并探索了潜在的生存标志物。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。对于一组标记物，DSP 分析物和传统免疫组织化学评分之间的相关分析显示，两种平台之间存在中度至非常强的相关性。同样，对于重叠的 25 个标记物中的 21 个标记物，DSP 分析物和基因表达评分是一致的。一些分析物因 ER 状态而异，在所调查的 25 个免疫标记物中，有 14 个与 ER 表达呈显著负相关。B7 同源物 3（B7-H3；由 CD276 编码）是唯一因种族而差异的分析物，在黑人女性的肿瘤和基质隔室中均较低。与生存相关的 DSP 标记物包括 CD8、CD25、CD56、CD127、EpCAM、ER、Ki-67 和 STING。我们得出的结论是，DSP 是一种同时筛选肿瘤和免疫相关标志物的有效工具，其结果与既定的免疫分析检测结果一致。DSP 免疫分析物与 ER 表达呈负相关，这与大量先前的研究一致，这些研究记录了 ER 阴性乳腺癌中更高的免疫浸润。这项技术表明，与白人女性相比，黑人女性的乳腺癌中 B7-H3 蛋白的评分明显更低，这是一个有趣的发现，需要在独立的、种族多样化的女性人群中进行复制。
