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垂体促肾上腺皮质激素细胞肿瘤的空间转录组分析

Spatial Transcriptomic Analysis of Pituitary Corticotroph Tumors.

作者信息

Piña Jeremie Oliver, Faucz Fabio R, Padilla Cameron, Floudas Charalampos S, Chittiboina Prashant, Quezado Martha, Tatsi Christina

机构信息

Section on Craniofacial Genetic Disorders, Eunice Kennedy ShriverNational Institute of Child Health, and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

Molecular Genomics Core, Eunice Kennedy ShriverNational Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

J Endocr Soc. 2024 Apr 3;8(6):bvae064. doi: 10.1210/jendso/bvae064. eCollection 2024 Apr 6.

Abstract

CONTEXT

Spatial transcriptomic (ST) analysis of tumors provides a novel approach to studying gene expression along with the localization of tumor cells in their environment to uncover spatial interactions.

DESIGN

We present ST analysis of corticotroph pituitary neuroendocrine tumors (PitNETs) from formalin-fixed, paraffin-embedded tissues. ST data were compared to immunohistochemistry results. Gene expression profiles were reviewed for cluster annotations, and differentially expressed genes were used for pathway analysis.

RESULTS

Seven tumors were used for ST analysis. In situ annotation of tumor tissue was inferred from the gene expression profiles and was in concordance with the annotation made by a pathologist. Furthermore, relative gene expression in the tumor corresponded to common protein staining used in the evaluation of PitNETs, such as reticulin and Ki-67 index. Finally, we identified intratumor heterogeneity; clusters within the same tumor may present with different transcriptomic profiles, unveiling potential intratumor cell variability.

CONCLUSION

Together, our results provide the first attempt to clarify the spatial cell profile in PitNETs.

摘要

背景

肿瘤的空间转录组学(ST)分析提供了一种新方法,可用于研究基因表达以及肿瘤细胞在其环境中的定位,以揭示空间相互作用。

设计

我们展示了对来自福尔马林固定、石蜡包埋组织的促肾上腺皮质激素垂体神经内分泌肿瘤(PitNETs)的ST分析。将ST数据与免疫组织化学结果进行比较。对基因表达谱进行聚类注释审查,并使用差异表达基因进行通路分析。

结果

七个肿瘤用于ST分析。从基因表达谱推断肿瘤组织的原位注释,并与病理学家做出的注释一致。此外,肿瘤中的相对基因表达与评估PitNETs时常用的蛋白质染色一致,如网硬蛋白和Ki-67指数。最后,我们确定了肿瘤内异质性;同一肿瘤内的簇可能呈现不同的转录组谱,揭示了潜在的肿瘤内细胞变异性。

结论

总之,我们的结果首次尝试阐明PitNETs中的空间细胞图谱。

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