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자료유형
학술저널
저자정보
김용휘 (서울대학교병원) 김정희 (서울대학교병원)
저널정보
대한내분비학회 Endocrinology and Metabolism Endocrinology and Metabolism Vol.34 No.3
발행연도
2019.1
수록면
314 - 322 (9page)

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Background: Invasive nonfunctioning pituitary adenomas (NFPAs) remain challenging due to their high complication rate and poorprognosis. We aimed to identify the distinctive molecular signatures of invasive NFPAs, compared with noninvasive NFPAs, usinggene expression profiling by RNA sequencing. Methods: We obtained frozen fresh tissue samples from 14 patients with NFPAs who underwent primary transsphenoidal surgery. Three non-invasive and 11 invasive NFPAs were used for RNA sequencing. The bioinformatics analysis included differential geneexpression, gene ontology analysis, and pathway analysis. Results: A total of 700 genes were differentially expressed (59 up-regulated and 641 down-regulated genes) between invasive andnon-invasive NFPAs (false discovery rate <0.1, and |fold change| ≥2). Using the down-regulated genes in invasive NFPAs, geneontology enrichment analyses and pathway analyses demonstrated that the local immune response was attenuated and that transforming growth factor-β (TGF-β) RII-initiated TGF-β signaling was down-regulated in invasive NFPAs. The overexpression of claudin-9 (CLDN9) and the down-regulation of insulin-like growth factor-binding protein 5 (IGFBP5), death-associated protein kinase 1(DAPK1), and tissue inhibitor of metalloproteinase-3 (TIMP3) may be related with invasiveness in NFPAs. Conclusion: Invasive NFPAs harbor different gene expression profiles relative to noninvasive NFPAs. In particular, local suppression of the immune response and TGF-β signaling can make PAs prone to invasiveness.

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