Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Department of Neurological Surgery, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Neuroendocrinology. 2024;114(7):670-680. doi: 10.1159/000539017. Epub 2024 Apr 23.
Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA).
Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from 3 patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA.
Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs.
This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations.
催乳素细胞垂体神经内分泌肿瘤(PitNETs)是常见的垂体肿瘤,但它们的潜在分子机制仍不清楚。本研究旨在通过 RNA 测序和 Ingenuity 通路分析(IPA),研究催乳素细胞 PitNETs 的转录组图谱,并确定潜在的分子机制和治疗靶点。
对五例未经多巴胺激动剂治疗的手术催乳素细胞 PitNET 组织进行 RNA 测序。以 3 例正常垂体组织作为对照。通过 IPA 识别差异表达基因(DEGs),并探讨其功能途径和基因网络。
转录组分析显示,催乳素细胞 PitNETs 的基因表达模式与正常垂体组织明显不同。我们共鉴定出 1172 个上调的 DEGs,其中包括 9 个属于前 30 个 DEGs 的长非编码 RNA(lncRNA)。上调 DEGs 的 IPA 分析表明,雌激素受体信号、氧化磷酸化信号和 EIF 信号被激活。在基因网络分析中,EGR1、PRKACA、PITX2、CREB1 和 JUND 等关键上游调节剂可能在催乳素细胞 PitNETs 中发挥重要作用。
本研究提供了催乳素细胞 PitNETs 的全面转录组图谱,并强调了 lncRNA 和特定信号通路在肿瘤发病机制中的潜在作用。鉴定出的上游调节剂可能是未来研究的潜在治疗靶点。