Abstract
Purpose: To explore the molecular mechanism and prognosis of bone-invasive pituitary adenomas (BIPA).Experimental design: 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.Results: 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. In vitro, 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.Conclusions: 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. Clin Cancer Res; 24(22); 5757-66. ©2018 AACR.
Highlights
Pituitary adenomas are benign tumors that originate in the anterior pituitary cells and account for approximately 8% to 15% of intracranial tumors [1, 2]
Inflammatory and immune factors play an important role in bone-invasive pituitary adenomas (BIPA)
We found that non-gross total resection (NGTR) and invasion were independent risk factors of pituitary adenomas, BIPAs had worse progression-free survival (PFS) than did non-bone-invasive pituitary adenomas (NBIPA) in the NGTR and nonfunctional pituitary adenoma (NFPA) groups
Summary
Pituitary adenomas are benign tumors that originate in the anterior pituitary cells and account for approximately 8% to 15% of intracranial tumors [1, 2]. Large pituitary adenomas are typically invasive and infiltrate the surrounding dura, sinus, brain, and bone tissue. There are few studies focused on the prognosis and mechanisms of bone-invasive pituitary adenomas (BIPA); most studies are clinical and imaging [3]. Because of its serious destruction of the surrounding bone mass and large size, the surgical resection of BIPAs is a significant challenge and may increase the potential risk of cerebrospinal fluid leaks. Based on these factors, it is important to explore and
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