Transcriptional Profiling of Pituitary Adenoma Stem Cells: Unveiling the Pivotal Role of CXCR4 in Tumorigenesis and Clinical Applications

Abstract Background Growth hormone-secreting pituitary adenoma (GHPA) is characterized by excessive growth hormone production and leads to clinical manifestations like acromegaly. The molecular intricacies underpinning the tumorigenesis of this neoplasm remain largely elusive, with tumor stem cells postulated to play a significant role. Method Human pituitary adenoma stem cells (hPASCs) were extracted and cultured from eight GHPA clinical samples. RNA-sequencing was performed to discern genetic disparities between hPASCs and matched bulk tumor samples. Primary clusters of protein-protein interaction network were mapped using MCODE plugin in Cytoscape. The functional role of CXCR4 was assessed by both siRNA and antagonist AMD3465 in GH3 cells or primary hPASCs. Seven GHPA patients received PET/CT scan using CXCR4-based tracer 68Ga-pentixafor. Results HPASC culture was established and verified. A total of 685 differentially expressed genes were identified between hPASC and bulk tumor samples. Four primary protein-protein interaction network clusters were predicted, each demonstrating distinct biological functions. CXCR4 knockdown significantly attenuated GH3 cell proliferation and the hormone production. CXCR4 antagonist AMD3465 markedly reduced cell proliferation during differentiation of hPASCs. PET/CT imaging showed 68Ga-pentixafor can be a superior tracer in the detection of GHPA in the patients. Conclusion This study delivers a comprehensive genetic profiling of hPASCs and substantiates the critical role of CXCR4 in tumorigenesis, highlighting its considerable diagnostic potential in the translational research.