{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:48:07Z","timestamp":1761061687595,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to investigate the metabolic differences between invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs), determine the expression of an M2 macrophage marker in NFPAs, and analyze the effects of metabolic changes in invasive NFPAs on M2 macrophage infiltrates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue samples of NFPAs from patients who underwent transsphenoidal or craniotomy surgery from January 2021 to August 2021 were collected. NFPA tissues were analyzed based on a gas chromatography-mass spectrometry non-targeted metabolomics platform, and immunohistochemical staining for M2 macrophage marker CD206 was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We evaluated 15 invasive and 21 non-invasive NFPAs. A total of 22 metabolites were identified through non-targeted metabolomics analysis. Among them, the expression of 1-octadecanol, inosine 5\u2019-monophosphate, adenosine 5\u2019-monophosphate, guanosine 5\u2019-monophosphate, creatinine, desmosterol, taurine, hypotaurine, lactic acid, and succinic acid was upregulated in invasive NFPAs, while that of 1-oleoylglycerol, arachidonic acid, cis-11-eicosenoic acid, docosahexaenoic acid, glyceric acid, hypoxanthine, linoleic acid, lysine, oleic acid, uracil, valine, and xanthine was downregulated. Immunohistochemical analysis suggested that the number of CD206-positive cells was higher in invasive NFPAs than in non-invasive NFPAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Invasive and non-invasive NFPAs showed distinct metabolite profiles. The levels of succinic acid and lactic acid were higher in invasive NFPAs, and the high expression of the M2 macrophage marker was verified in invasive NFPAs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.901884","type":"journal-article","created":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T21:24:50Z","timestamp":1657488290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Metabolic Characteristics and M2 Macrophage Infiltrates in Invasive Nonfunctioning Pituitary Adenomas"],"prefix":"10.3389","volume":"13","author":[{"given":"Kunzhe","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Pei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shousen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"iii1","DOI":"10.1093\/neuonc\/noab200","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018","volume":"23","author":"Ostrom","year":"2021","journal-title":"Neuro Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-20-3446","article-title":"Pituitary Adenoma or Pituitary Neuroendocrine Tumor: A Narrative Review of Controversy and Perspective","volume":"10","author":"Liu","year":"2021","journal-title":"Transl Cancer Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.785050","article-title":"Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches","volume":"12","author":"Han","year":"2021","journal-title":"Front Endocrinol (Lausanne)."},{"key":"B4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00701-017-3396-5","article-title":"Early Recognition of Aggressive Pituitary Adenomas: A Single-Centre Experience","volume":"160","author":"Ceccato","year":"2018","journal-title":"Acta Neurochir (Wien)."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7150\/thno.53749","article-title":"Lactate-Induced M2 Polarization of Tumor-Associated Macrophages Promotes the Invasion of Pituitary Adenoma by Secreting CCL17","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00814","article-title":"Metabolomics-A Promising Approach to Pituitary Adenomas","volume":"9","author":"P\u00eenzariu","year":"2018","journal-title":"Front Endocrinol (Lausanne)."},{"key":"B7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab"},{"key":"B8","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3390\/metabo11010028","article-title":"Metabolic Reprogramming of Cancer Cells During Tumor Progression and Metastasis","volume":"11","author":"Ohshima","year":"2021","journal-title":"Metabolites."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188427","article-title":"Oncometabolites Lactate and Succinate Drive Pro-Angiogenic Macrophage Response in Tumors","volume":"1874","author":"Kes","year":"2020","journal-title":"Biochim Biophys Acta Rev Cancer."},{"key":"B10","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3390\/metabo10120478","article-title":"Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses","volume":"10","author":"Yu","year":"2020","journal-title":"Metabolites."},{"key":"B11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/s12967-019-2042-9","article-title":"Metabolic Profiling Reveals Distinct Metabolic Alterations in Different Subtypes of Pituitary Adenomas and Confers Therapeutic Targets","volume":"17","author":"Feng","year":"2019","journal-title":"J Transl Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12943-021-01316-8","article-title":"The Cancer Metabolic Reprogramming and Immune Response","volume":"20","author":"Xia","year":"2021","journal-title":"Mol Cancer."},{"key":"B13","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.molcel.2019.10.023","article-title":"Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor","volume":"77","author":"Wu","year":"2020","journal-title":"Mol Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6031670","article-title":"Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment","volume":"6","author":"Chanmee","year":"2014","journal-title":"Cancers (Basel)."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-015-9383-6","article-title":"Immune Cell Infiltrates in Pituitary Adenomas: More Macrophages in Larger Adenomas and More T Cells in Growth Hormone Adenomas","volume":"26","author":"Lu","year":"2015","journal-title":"Endocr Pathol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-020-03476-x","article-title":"In Silico Analysis of the Immunological Landscape of Pituitary Adenomas","volume":"147","author":"Yeung","year":"2020","journal-title":"J Neurooncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1227\/00006123-199310000-00008","article-title":"Pituitary Adenomas With Invasion of the Cavernous Sinus Space: A Magnetic Resonance Imaging Classification Compared With Surgical Findings","volume":"33","author":"Knosp","year":"1993","journal-title":"Neurosurgery."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01639-8","article-title":"The Functional Roles of TCA Cycle Metabolites in Cancer","volume":"40","author":"Eniafe","year":"2021","journal-title":"Oncogene."},{"key":"B19","doi-asserted-by":"publisher","first-page":"R246","DOI":"10.1016\/j.cub.2020.01.031","article-title":"Tumor-Associated Macrophages","volume":"30","author":"Cassetta","year":"2020","journal-title":"Curr Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/s13402-019-00453-z","article-title":"Tumor-Associated Macrophages: Role in Cancer Development and Therapeutic Implications","volume":"42","author":"Salmaninejad","year":"2019","journal-title":"Cell Oncol (Dordr)."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4103\/2319-4170.131378","article-title":"Anti-Cancer Activities of \u03c9-6 Polyunsaturated Fatty Acids","volume":"37","author":"Xu","year":"2014","journal-title":"BioMed J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/310186","article-title":"Dietary \u03c9 -3 Polyunsaturated Fatty Acid DHA: A Potential Adjuvant in the Treatment of Cancer","volume":"2013","author":"Merendino","year":"2013","journal-title":"BioMed Res Int"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1482.147702","article-title":"Differences of Polyunsaturated Fatty Acid in Patients With Colorectal Cancer and Healthy People","volume":"11","author":"Wang","year":"2015","journal-title":"J Cancer Res Ther"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1016\/j.cmet.2021.05.016","article-title":"Peroxidation of N-3 and N-6 Polyunsaturated Fatty Acids in the Acidic Tumor Environment Leads to Ferroptosis-Mediated Anticancer Effects","volume":"33","author":"Dierge","year":"2021","journal-title":"Cell Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01697","article-title":"Potential Mechanisms Connecting Purine Metabolism and Cancer Therapy","volume":"9","author":"Yin","year":"2018","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-51652-9_18","article-title":"Metabolomics of Glioma","volume":"1280","author":"Feng","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4537","article-title":"Purine Synthesis Promotes Maintenance of Brain Tumor Initiating Cells in Glioma","volume":"20","author":"Wang","year":"2017","journal-title":"Nat Neurosci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30829","article-title":"Global and Targeted Serum Metabolic Profiling of Colorectal Cancer Progression","volume":"123","author":"Long","year":"2017","journal-title":"Cancer."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-181500","article-title":"Taurine, Glutamic Acid and Ethylmalonic Acid as Important Metabolites for Detecting Human Breast Cancer Based on the Targeted Metabolomics","volume":"23","author":"Wang","year":"2018","journal-title":"Cancer biomark"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00351","article-title":"Distinct Metabolomic Profiles of Papillary Thyroid Carcinoma and Benign Thyroid Adenoma","volume":"14","author":"Xu","year":"2015","journal-title":"J Proteome Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1021\/pr100176g","article-title":"Discrimination of Patients With Microsatellite Instability Colon Cancer Using 1H HR MAS MR Spectroscopy and Chemometric Analysis","volume":"9","author":"Tessem","year":"2010","journal-title":"J Proteome Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-020-02836-7","article-title":"Metabolomics Analysis Identifies Lysine and Taurine as Candidate Prognostic Biomarkers for AML-M2 Patients","volume":"111","author":"Zhou","year":"2020","journal-title":"Int J Hematol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-33504-9_47","article-title":"Taurine Concentration in Human Gliomas and Meningiomas: Tumoral, Peritumoral, and Extratumoral Tissue","volume":"583","author":"Cubillos","year":"2006","journal-title":"Adv Exp Med Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/0014-5793(87)80411-8","article-title":"The Mechanism of Neuronal Resistance and Adaptation to Hypoxia","volume":"224","author":"Schurr","year":"1987","journal-title":"FEBS Lett"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0867-9","article-title":"The Evolving Role of Taurolidine in Cancer Therapy","volume":"17","author":"Neary","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7710","article-title":"Hypotaurine Evokes a Malignant Phenotype in Glioma Through Aberrant Hypoxic Signaling","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget."}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.901884\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T21:24:53Z","timestamp":1657488293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.901884\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":36,"alternative-id":["10.3389\/fendo.2022.901884"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.901884","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2022,7,8]]},"article-number":"901884"}}