Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, China.
Clin Cancer Res. 2018 Nov 15;24(22):5757-5766. doi: 10.1158/1078-0432.CCR-18-0472. Epub 2018 Jul 6.
To explore the molecular mechanism and prognosis of bone-invasive pituitary adenomas (BIPA). A total of 274 patients with pituitary adenomas were followed up. Transcriptomic microarrays analysis was performed on 10 pituitary adenomas, including five BIPAs and five non-bone-invasive pituitary adenomas (NBIPA). The targeted molecular markers were validated by qRT-PCR, IHC, ELISA, and osteoclast differentiation. Clinical variable analyses revealed a significant correlation between bone invasion and female sex, large tumor volume, non-gross total resection (NGTR), and tumor regrowth. BIPAs had worse progression-free survival (PFS) than did NBIPAs in the NGTR and nonfunctional pituitary adenoma (NFPA) groups. Gene ontology functional and KEGG pathway analyses showed that the biological processes and pathways were primarily immune and inflammatory pathways. Pathway act work showed that osteoclast differentiation pathway was significantly implicated in the pathway network. BIPAs had higher expression of TNFα than that of NBIPAs on IHC. , TNFα could induce RAW264.7 cells to differentiate into mature osteoclasts, leading to bone destruction. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression. BIPAs had worse PFS than did NBIPAs in the NGTR and NFPA groups. Inflammatory and immune factors play an important role in BIPAs. TNFα can directly induce osteoclast differentiation in BIPAs. NR_033258, lncRNA SNHG24, miR-181c-5p, and miR-454-3p can regulate TNFα expression. TNFα and its related lncRNAs and miRNAs represent potential therapeutic targets for bone-invasive pituitary adenomas in the future. .
探讨骨侵袭性垂体腺瘤（BIPA）的分子机制和预后。对 274 例垂体腺瘤患者进行随访。对 10 例垂体腺瘤（包括 5 例 BIPA 和 5 例非骨侵袭性垂体腺瘤（NBIPA））进行转录组微阵列分析。通过 qRT-PCR、IHC、ELISA 和破骨细胞分化验证靶向分子标志物。临床变量分析显示，骨侵袭与女性、大肿瘤体积、非大体全切除（NGTR）和肿瘤复发显著相关。在 NGTR 和无功能垂体腺瘤（NFPA）组中，BIPA 的无进展生存期（PFS）明显劣于 NBIPA。GO 功能和 KEGG 通路分析显示，生物学过程和通路主要为免疫和炎症通路。通路活性分析显示，破骨细胞分化通路在通路网络中显著相关。IHC 显示，BIPA 的 TNFα 表达高于 NBIPA。TNFα 可诱导 RAW264.7 细胞分化为成熟破骨细胞，导致骨质破坏。NR_033258、lncRNA SNHG24、miR-181c-5p 和 miR-454-3p 可调节 TNFα 表达。在 NGTR 和 NFPA 组中，BIPA 的 PFS 明显劣于 NBIPA。炎症和免疫因素在 BIPA 中起重要作用。TNFα 可直接诱导 BIPA 中的破骨细胞分化。NR_033258、lncRNA SNHG24、miR-181c-5p 和 miR-454-3p 可调节 TNFα 表达。TNFα 及其相关 lncRNAs 和 miRNAs 可能成为未来骨侵袭性垂体腺瘤的潜在治疗靶点。
