title: Integrative proteomics and transcriptomics revealed that activation of the IL-6R/JAK2/STAT3/MMP9 signaling pathway is correlated with invasion of pituitary null cell adenomas.
abstract: Non-functioning pituitary adenomas (NFPAs) are a highly heterogeneous group, but few studies have explored the invasion mechanism of specific subtypes of NFPAs. The objective of this study was to investigate the differential molecular expression patterns and the critical biological signaling pathways involved in the invasion of pituitary null cell adenomas (PNCAs) through integrative proteomics and transcriptomics. A total of 1160 genes and 283 proteins were found to be differentially expressed in invasive and non-invasive PNCAs. The differentially expressed molecules related to invasion were enriched in 15 canonical signaling pathways, 15 clusters of diseases or biological functions and 5 upstream molecules. Among them, the majority of the differentially expressed molecules were found to be involved in transport of molecule, migration of cells and cell movement. Notably, IL-6 was a significantly activated upstream regulator, and the IL6R/JAK2/STAT3 cascade was found to play a critical role in acute phase response signaling, which was the most significant canonical signaling pathway. Furthermore, we validated the overexpression of IL-6R, JAK2, STAT3, p-STAT3 and MMP9 in invasive PNCAs. Our data suggest that overactivation of the IL-6R/JAK2/STAT3/MMP9 pathway is critical for the invasion of PNCAs.
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China; Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Yu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China.
authors.forename: Chu-Zhong
authors.initials: CZ
authors.lastname: Li
authors.affiliation: Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Zhen-Ye
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China. Electronic address: zyz2004520@yeah.net.
authors.forename: Ya-Zhuo
authors.initials: YZ
authors.lastname: Zhang
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015203:Reproducibility of Results; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2; D020780:Matrix Metalloproteinase 9
keywords: IL-6R; Invasion; JAK2; Null cell adenomas; Pituitary adenomas; STAT3