High-Plex Spatial RNA Profiling Reveals Cell Type‒Specific Biomarker Expression during Melanoma Development.
High-Plex Spatial RNA Profiling Reveals Cell Type‒Specific Biomarker Expression during Melanoma Development.
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DOI：
10.1016/j.jid.2021.06.041
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发表时间：
2022-05
影响因子：
6.5
通讯作者：
McPherson, John D.
中科院分区：
文献类型：
--
作者：
Kiuru, Maija;Kriner, Michelle A.;Wong, Samantha;Zhu, Guannan;Terrell, Jessica R.;Li, Qian;Hoang, Margaret;Beechem, Joseph;McPherson, John D.
黑色素瘤的早期诊断对于提高生存率至关重要。然而，早期黑色素瘤演变的生物标志物及其在肿瘤及其微环境（包括角质形成细胞）中的起源尚不清楚。为了解决这个问题，我们使用了维持肿瘤形态学背景的空间转录谱分析，以在原发性黑色素瘤和黑色素细胞痣中的患者来源的福尔马林固定的石蜡包埋组织切片中原位测量> 1，000个RNA的表达。我们分析了134个200μ m直径的目标区域，这些区域富含黑素细胞、邻近的角质形成细胞或免疫细胞。这种方法在黑色素瘤发展过程中捕获了不同细胞类型和肿瘤类型的不同表达模式。出乎意料的是，我们发现S100A8在黑色素瘤生长期间由肿瘤微环境内的角质形成细胞表达。252例肿瘤的免疫组化显示，在黑色素瘤中显著的角化细胞来源的S100A8表达，但在良性肿瘤中没有，并证实了S100A8的结合伴侣S100A9的相同模式，这表明表皮损伤可能是黑色素瘤发展的早期和容易检测的指标。总之，我们的研究结果建立了一个框架，用于存档组织中基因表达的高复杂性，空间和细胞类型特异性分辨率，适用于肿瘤演变中肿瘤微环境相互作用的生物标志物和表征的开发。
Early diagnosis of melanoma is critical for improved survival. However, biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment, including the keratinocytes, are poorly defined. To address this, we used spatial transcript profiling that maintains the morphological tumor context to measure expression of >1,000 RNAs in situ in patient-derived formalin-fixed, paraffin-embedded tissue sections in primary melanoma and melanocytic nevi. We profiled 134 200µm-diameter regions of interest enriched in melanocytes, neighboring keratinocytes or immune cells. This approach captured distinct expression patterns across cell types and tumor types during melanoma development. Unexpectedly, we discovered that S100A8 is expressed by keratinocytes within the tumor microenvironment during melanoma growth. Immunohistochemistry of 252 tumors showed prominent keratinocyte-derived S100A8 expression in melanoma but not in benign tumors and confirmed the same pattern for S100A8’s binding partner S100A9, suggesting that injury to the epidermis may be an early and readily detectable indicator of melanoma development. Together, our results establish a framework for high-plex, spatial and cell type-specific resolution of gene expression in archival tissue applicable to the development of biomarkers and characterization of tumor-microenvironment interactions in tumor evolution.
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影响因子：
46.9
作者：
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