Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China.
Acta Neuropathol Commun. 2023 Feb 7;11(1):24. doi: 10.1186/s40478-023-01517-w.
Gonadotrophic pituitary adenoma is a major subtype of pituitary adenoma in the sellar region, but it is rarely involved in the hypersecretion of hormones into blood; thus, it is commonly regarded as "non-functioning." Its tumorigenic mechanisms remain unknown. The aim of this study was to identify human gonadotrophic pituitary adenoma stem cells (hPASCs) and explore the underlying gene expression profiles. In addition, the potential candidate genes involved in the invasive properties of pituitary adenoma were examined.
The hPASCs from 14 human gonadotrophic pituitary adenoma clinical samples were cultured and verified via immunohistochemistry. Genetic profiling of hPASCs and the matched tumor cells was performed through RNA-sequencing and subjected to enrichment analysis. By aligning the results with public databases, the candidate genes were screened and examined in invasive and non-invasive gonadotrophic pituitary adenomas using Real-time polymerase chain reaction.
The hPASCs were successfully isolated and cultured from gonadotrophic pituitary adenoma in vitro, which were identified as positive for generic stem cell markers (Sox2, Oct4, Nestin and CD133) via immunohistochemical staining. The hPASCs could differentiate into the tumor cells expressing follicle-stimulating hormone in the presence of fetal bovine serum in the culture medium. Through RNA-sequencing, 1352 differentially expressed genes were screened and identified significantly enriched in various gene ontologies and important pathways. The expression levels of ANXA2, PMAIP1, SPRY2, C2CD4A, APOD, FGF14 and FKBP10 were significantly upregulated while FNDC5 and MAP3K4 were downregulated in the invasive gonadotrophic pituitary adenomas compared to the non-invasive ones.
Genetic profiling of hPASCs may explain the tumorigenesis and invasiveness of gonadotrophic pituitary adenoma. ANXA2 may serve as a potential therapeutic target for the treatment of gonadotrophic pituitary adenoma.
促性腺激素型垂体腺瘤是鞍区垂体腺瘤的主要亚型，但它很少参与血液中激素的过度分泌；因此，通常被认为是“无功能的”。其肿瘤发生机制尚不清楚。本研究旨在鉴定人促性腺激素型垂体腺瘤干细胞（hPASCs），并探讨其潜在的基因表达谱。此外，还研究了潜在的候选基因在垂体腺瘤侵袭性中的作用。
从 14 例人促性腺激素型垂体腺瘤临床样本中培养并通过免疫组织化学验证 hPASCs。通过 RNA-seq 对 hPASCs 和匹配的肿瘤细胞进行基因谱分析，并进行富集分析。通过与公共数据库对齐，筛选候选基因，并通过实时聚合酶链反应在侵袭性和非侵袭性促性腺激素型垂体腺瘤中进行检测。
成功地从体外培养的促性腺激素型垂体腺瘤中分离和培养出 hPASCs，通过免疫组织化学染色鉴定其为通用干细胞标志物（Sox2、Oct4、Nestin 和 CD133）阳性。在含有胎牛血清的培养基中，hPASCs 可以分化为表达促卵泡激素的肿瘤细胞。通过 RNA-seq 筛选出 1352 个差异表达基因，并鉴定出其在各种基因本体论和重要途径中显著富集。与非侵袭性促性腺激素型垂体腺瘤相比，侵袭性促性腺激素型垂体腺瘤中 ANXA2、PMAIP1、SPRY2、C2CD4A、APOD、FGF14 和 FKBP10 的表达水平显著上调，而 FNDC5 和 MAP3K4 的表达水平下调。
hPASCs 的基因谱分析可能解释了促性腺激素型垂体腺瘤的发生和侵袭性。ANXA2 可能成为治疗促性腺激素型垂体腺瘤的潜在治疗靶点。
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