Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China.
J Transl Med. 2024 Oct 3;22(1):892. doi: 10.1186/s12967-024-05702-w.
Pituitary adenomas (PAs) are the second most common intracranial tumor. While current diagnostic practices rely primarily on histological testing, they often fail to capture the molecular complexities of pituitary adenomas, underscoring the need for a molecular-based classification to refine therapeutic strategies and prognostic assessments. This study aims to provide a molecularly unbiased classification of pituitary adenomas and explore their unique gene expression patterns and clinical features.
We performed unsupervised hierarchical clustering of the gene expression profiles of 117 PA samples to identify three distinct molecular subtypes. Subsequently, we analyzed the compiled transcriptomic profiles of each individual subtype for pathway enrichment. We also validated the new classification with a validation set containing 158 PAs and 24 pituitary adenoma stem cells (PASCs).
Consensus clustering of transcriptomic data from 117 pituitary adenoma (PA) samples identified three distinct molecular subtypes, each showing unique gene expression patterns and associated biological processes: Group I is enriched in signaling pathways, such as the cAMP signaling pathway and the calcium signaling pathway. Group II is primarily related to metabolic processes, including nitrogen metabolism and arginine biosynthesis in cancer. Group III predominantly shows enrichment in immune responses and potential malignant transformation of the disease, especially through cancer-related pathways such as the JAK-STAT signaling pathway and the PI3K-Akt signaling pathway. The immune profiling revealed distinct patterns for each subtype: Group I had higher dendritic cells and fewer CD8+ T cells, Group II had more monocytes and macrophages, and Group III had elevated levels of T cells. Additionally, there were differences in clinical characteristics and prognosis among the subtypes, with Group III having a worse prognosis, despite the smaller tumor size compared to other groups. Notably, differences in PASCs correlated with the molecular subtypes, with Group III stem cells being enriched in tumorigenesis pathways, PI3K-Akt signaling pathway and Ras signaling pathway.
Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.
垂体腺瘤（PA）是第二常见的颅内肿瘤。虽然目前的诊断实践主要依赖于组织学检测，但它们往往无法捕捉到垂体腺瘤的分子复杂性，这凸显了需要一种基于分子的分类方法来完善治疗策略和预后评估。本研究旨在对垂体腺瘤进行无偏倚的分子分类，并探索其独特的基因表达模式和临床特征。
我们对 117 例 PA 样本的基因表达谱进行无监督层次聚类，以鉴定出三个不同的分子亚型。随后，我们分析了每个亚型的综合转录组谱，以确定通路富集情况。我们还使用包含 158 例 PA 和 24 例垂体腺瘤干细胞（PASC）的验证集来验证新分类。
对 117 例垂体腺瘤（PA）样本的转录组数据进行一致性聚类，鉴定出三个不同的分子亚型，每个亚型均表现出独特的基因表达模式和相关的生物学过程：I 组富含信号通路，如 cAMP 信号通路和钙信号通路。II 组主要与代谢过程相关，包括氮代谢和癌症中的精氨酸生物合成。III 组主要表现出对免疫反应的富集，以及疾病的潜在恶性转化，特别是通过癌症相关通路，如 JAK-STAT 信号通路和 PI3K-Akt 信号通路。免疫分析显示每个亚型都有不同的模式：I 组树突细胞较多，CD8+T 细胞较少；II 组单核细胞和巨噬细胞较多；III 组 T 细胞水平升高。此外，各亚型之间的临床特征和预后存在差异，尽管 III 组肿瘤较小，但预后较差。值得注意的是，PASC 中的差异与分子亚型相关，III 组干细胞在肿瘤发生途径、PI3K-Akt 信号通路和 Ras 信号通路中富集。
本研究提出了一种新的垂体腺瘤分子分类方法，与传统的组织学方法无关。每个亚型都具有独特的遗传、分子和免疫学特征。我们已经分离出垂体腺瘤干细胞样细胞（PASC），并将其与肿瘤组织配对进行详细的转录组分析。这些 PASC 表现出与新分类一致的多种分子特征。
