Evidence of Significant Intratumoral Transcriptomic Heterogeneity in Non-functioning Pituitary Adenomas Based on Location and Texture.

Introduction Surgical resection remains a standard treatment of non-functioning pituitary adenomas (NFPA). These tumors have significant intratumoral variability of growth rates and texture hardness. This preliminary study aims to identify variations in gene expression of different locations and textures within the same tumor to better explain tumor pathophysiology. Methods NFPA tissue samples were collected from four non-consecutive surgical adult patients undergoing endoscopic endonasal resection and were sent for next-generation transcriptomics. Significantly differentially expressed (SDE) genes were analyzed and categorized using ontology within different locations of the tumor, tumor hardness, and across patients. Results Around 164 SDE genes were identified: 264 across tumor hardness and 68 across location marginality (core vs. edge). A total of 132 gene ontology annotations were matched to all SDE genes. Most of these annotations involved a combination of cell metabolism, cell-cell interactions, and cell division. Conclusions There was significant evidence of variations and uniqueness in intratumor genetic heterogeneity within different locations, tumor textures, and across patients. The tumor edge expressed higher cell-cell interaction genes such as cadherin-binding proteins. Soft portions of the tumor experienced an upregulation of anaerobic metabolism and cell division genes. The uniqueness of gene expressions can be tested for biological function, prospectively, with the potential targets for gene therapy.