Spatial Transcriptomic Analysis of Pituitary Corticotroph Tumors

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.

Keywords: Cushing disease; pituitary neuroendocrine tumor; spatial transcriptomics.