{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T06:40:03Z","timestamp":1777185603109,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,2]],"date-time":"2022-10-02T00:00:00Z","timestamp":1664668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Meningiomas are mostly benign tumors that, at times, can behave aggressively, displaying recurrence despite gross-total resection (GTR) and progression to overt malignancy. Such cases represent a clinical challenge, particularly because they are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription factor with a key role in stem cell maintenance and has been associated with tumorigenesis in a variety of cancers. The purpose of the present work was to dissect the role of SOX2 in predicting the aggressiveness of meningioma. We analyzed progressive\/recurrent WHO grade 1\u20132 meningiomas and WHO grade 3 meningiomas; as controls, non-recurring WHO grade 1 and grade 2 meningioma patients were enrolled. SOX2 expression was evaluated using both immunohistochemistry (IHC) and RT-PCR. The final analysis included 87 patients. IHC was able to reliably assess SOX2 expression, as shown by the good correlation with mRNA levels (Spearman R = 0.0398, p = 0.001, AUC 0.87). SOX2 expression was an intrinsic characteristic of any single tumor and did not change following recurrence or progression. Importantly, SOX2 expression at first surgery was strongly related to meningioma clinical behavior, histological grade and risk of recurrence. Finally, survival data suggest a prognostic role of SOX2 expression in the whole series, both for overall and for recurrence-free survival (p &lt; 0.0001 and p = 0.0001, respectively). Thus, SOX2 assessment could be of great help to clinicians in informing adjuvant treatments during follow-up.<\/jats:p>","DOI":"10.3390\/ijms231911690","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Dissecting Stemness in Aggressive Intracranial Meningiomas: Prognostic Role of SOX2 Expression"],"prefix":"10.3390","volume":"23","author":[{"given":"Rina","family":"Di Bonaventura","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6260-6310","authenticated-orcid":false,"given":"Maurizio","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-4587","authenticated-orcid":false,"given":"Tonia","family":"Cenci","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio Maria","family":"Caccavella","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-1920","authenticated-orcid":false,"given":"Valeria","family":"Barresi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Universit\u00e0 di Verona, 37129 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Gessi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Albanese","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-055X","authenticated-orcid":false,"given":"Liverana","family":"Lauretti","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-8827","authenticated-orcid":false,"given":"Roberto","family":"Pallini","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2953-9291","authenticated-orcid":false,"given":"Quintino Giorgio","family":"D'Alessandris","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Olivi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione Policlinico Agostino Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.humpath.2018.07.035","article-title":"Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur","volume":"84","author":"Navarro","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/jnen\/nlaa018","article-title":"A Risk Score Based on 5 Clinico-Pathological Variables Predicts Recurrence of Atypical Meningiomas","volume":"79","author":"Fioravanzo","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14115","DOI":"10.1038\/s41598-020-70514-z","article-title":"Programmed death ligand-1 (PD-L1) expression in meningioma; prognostic significance and its association with hypoxia and NFKB2 expression","volume":"10","author":"Karimi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_4","unstructured":"WHO Classification of Tumours Editorial Board (2021). Central Nervous System Tumours."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.yexmp.2010.12.003","article-title":"Isolation and characterization of a population of stem-like progenitor cells from an atypical meningioma","volume":"90","author":"Rath","year":"2011","journal-title":"Exp. Mol. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fsurg.2018.00065","article-title":"Expression of Embryonic Stem Cell Markers on the Microvessels of WHO Grade I Meningioma","volume":"5","author":"Shivapathasundram","year":"2018","journal-title":"Front. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jocn.2017.10.059","article-title":"Tumour stem cells in meningioma: A review","volume":"47","author":"Shivapathasundram","year":"2018","journal-title":"J. Clin. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1158\/1078-0432.CCR-08-0644","article-title":"Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme","volume":"14","author":"Pallini","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.semcancer.2019.08.007","article-title":"SOX2 in development and cancer biology","volume":"67","author":"Novak","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2174\/1389203720666190325102255","article-title":"Sox2: A Regulatory Factor in Tumorigenesis and Metastasis","volume":"20","author":"Chaudhary","year":"2019","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.semcancer.2019.03.004","article-title":"The role of SOX family members in solid tumours and metastasis","volume":"67","author":"Grimm","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/glia.23914","article-title":"Sox2-dependent maintenance of mouse oligodendroglioma involves the Sox2-mediated downregulation of Cdkn2b, Ebf1, Zfp423, and Hey2","volume":"69","author":"Barone","year":"2021","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41467-020-20194-0","article-title":"Structural basis for nuclear import selectivity of pioneer transcription factor SOX2","volume":"12","author":"Jagga","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.jiph.2019.03.015","article-title":"Correlation between SOX2 and Survivin clinical features in patients with salivary adenoid cystic carcinoma","volume":"12","author":"Luo","year":"2019","journal-title":"J. Infect. Public Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/sj.bjc.6603696","article-title":"Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy","volume":"96","author":"Schmitz","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/02688697.2021.1940853","article-title":"Biomarkers for differentiating grade II meningiomas from grade I: A systematic review","volume":"35","author":"Sofela","year":"2021","journal-title":"Br. J. Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3171\/jns.2004.101.2.0210","article-title":"Malignant progression in meningioma: Documentation of a series and analysis of cytogenetic findings","volume":"101","author":"Kadri","year":"2004","journal-title":"J. Neurosurg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"djv370","DOI":"10.1093\/jnci\/djv377","article-title":"TERT Promoter Mutations and Risk of Recurrence in Meningioma","volume":"108","author":"Sahm","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/neuonc\/noz061","article-title":"DNA methylation profiling to predict recurrence risk in meningioma: Development and validation of a nomogram to optimize clinical management","volume":"21","author":"Nassiri","year":"2019","journal-title":"Neuro-Oncology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1002\/mc.22653","article-title":"NANOG overexpression and its correlation with stem cell and differentiation markers in meningiomas of different WHO grades","volume":"56","author":"Freitag","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1242\/dev.091793","article-title":"Sox proteins: Regulators of cell fate specification and differentiation","volume":"140","author":"Kamachi","year":"2013","journal-title":"Development"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2217\/cns-2016-0001","article-title":"Sox2: Regulation of expression and contribution to brain tumors","volume":"5","author":"Mansouri","year":"2016","journal-title":"CNS Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.stem.2009.08.018","article-title":"Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors","volume":"5","author":"Ikushima","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1634\/stemcells.2008-0493","article-title":"SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity","volume":"27","author":"Gangemi","year":"2009","journal-title":"Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1158\/0008-5472.CAN-13-1407","article-title":"Targeting a glioblastoma cancer stem-cell population defined by EGF receptor variant III","volume":"74","author":"Emlet","year":"2014","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neo.2014.03.006","article-title":"Sox2 promotes malignancy in glioblastoma by regulating plasticity and astrocytic differentiation","volume":"16","author":"Berezovsky","year":"2014","journal-title":"Neoplasia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/PAS.0b013e31812f6ba6","article-title":"Sox2 expression in brain tumors: A reflection of the neuroglial differentiation pathway","volume":"32","author":"Phi","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lengerke, C., Fehm, T., Kurth, R., Neubauer, H., Scheble, V., M\u00fcller, F., Schneider, F., Petersen, K., Wallwiener, D., and Kanz, L. (2011). Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-42"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7663","DOI":"10.3390\/ijms13067663","article-title":"Expression of Sox2 and Oct4 and their clinical significance in human non-small-cell lung cancer","volume":"13","author":"Li","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fang, X., Yoon, J.-G., Li, L., Yu, W., Shao, J., Hua, D., Zheng, S., Hood, L., Goodlett, D.R., and Foltz, G. (2011). The SOX2 response program in glioblastoma multiforme: An integrated ChIP-seq, expression microarray, and microRNA analysis. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-11"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21557","DOI":"10.1038\/srep21557","article-title":"Metabolic\/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome","volume":"6","author":"Marziali","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/neuonc\/noy137","article-title":"Proposed response assessment and endpoints for meningioma clinical trials: Report from the Response Assessment in Neuro-Oncology Working Group","volume":"21","author":"Huang","year":"2019","journal-title":"Neuro-Oncology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:41Z","timestamp":1760143541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,2]]},"references-count":32,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911690"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911690","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,2]]}}}