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Res."],"abstract":"<jats:p>Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. In this study, VM-positive cases were detected in 28 (20.6%) out of 136 oligodendroglioma samples, significantly associated with higher WHO grade, lower Karnofsky performance status (KPS) scores, and recurrent tumor (<jats:italic>p<\/jats:italic> &amp;lt; 0.001, <jats:italic>p<\/jats:italic> = 0.040, and <jats:italic>p<\/jats:italic> = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), whereas no significant difference was detected in overall survival (OS) between these patients. High levels of phosphorylate serine\/threonine kinases Ataxia-telangiectasia mutated (pATM) and phosphorylate Ataxia-telangiectasia and Rad3-Related (pATR) were detected in 31 (22.8%) and 34 (25.0%), respectively out of 136 oligodendroglioma samples. Higher expressions of pATM and pATR were both associated with a shorter PFS (<jats:italic>p<\/jats:italic> &amp;lt; 0.001 and <jats:italic>p<\/jats:italic> &amp;lt; 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (r<jats:sub>s<\/jats:sub> = 0.435, <jats:italic>p<\/jats:italic> &amp;lt; 0.001 and r<jats:sub>s<\/jats:sub> = 0.317, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Besides, Hypoxia-inducible factor-1\u03b1 (HIF1\u03b1) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe (<jats:italic>p<\/jats:italic> = 0.010 and <jats:italic>p<\/jats:italic> = 0.029). However, no obvious connection was detected between HIF1\u03b1 expression and VM formation (<jats:italic>p<\/jats:italic> = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients (<jats:italic>p<\/jats:italic> &amp;lt; 0.001, HR = 7.928, 95%CI: 3.382\u201318.584, and <jats:italic>p<\/jats:italic> = 0.007, HR = 4.534, 95%CI: 1.504\u201313.675, respectively). VM is a potential prognosticator for tumor progression in oligodendroglioma patients. Phosphorylation of ATM and ATR linked to treatment-resistance may be associated with VM formation. The role of VM in tumor progression and the implication of pATM\/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment.<\/jats:p>","DOI":"10.3389\/pore.2021.1609844","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T04:20:34Z","timestamp":1629260434000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma"],"prefix":"10.3389","volume":"27","author":[{"given":"Jing","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenchao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/nan.12432","article-title":"WHO 2016 Classification of Gliomas","volume":"44","author":"Wesseling","year":"2018","journal-title":"Neuropathol Appl Neurobiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1007\/s00401-015-1424-1","article-title":"Oligodendroglioma: Pathology, Molecular Mechanisms and Markers","volume":"129","author":"Wesseling","year":"2015","journal-title":"Acta Neuropathol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s11912-009-0010-x","article-title":"Molecular Profiling of Oligodendrogliomas: Impact on Prognosis, Treatment, and Future Directions","volume":"11","author":"Ney","year":"2009","journal-title":"Curr Oncol Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11060-015-1906-y","article-title":"Prognostic Significance of Relative 1p\/19q Codeletion in Oligodendroglial Tumors","volume":"125","author":"Chamberlain","year":"2015","journal-title":"J Neurooncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/B978-0-12-802997-8.00022-0","article-title":"Low-grade and Anaplastic Oligodendroglioma","volume":"134","author":"Van Den Bent","year":"2016","journal-title":"Handb Clin Neurol"},{"key":"B6","first-page":"973","article-title":"Vessel Morphometric Parameters-Correlation with Histologic Grade and VEGF Expression in Oligodendroglioma","volume":"7","author":"Strickland-Marmol","year":"2017","journal-title":"Am J Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s11060-009-9961-x","article-title":"Assessment of Tumor Angiogenesis as a Prognostic Factor of Survival in Patients with Oligodendroglioma","volume":"96","author":"Quon","year":"2010","journal-title":"J Neurooncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1177\/1078155216681191","article-title":"Clinical Effectiveness of Bevacizumab in Patients with Recurrent Brain Tumours: A Population-Based Evaluation","volume":"24","author":"de Lemos","year":"2018","journal-title":"J Oncol Pharm Pract"},{"key":"B9","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/S0002-9440(10)65173-5","article-title":"Vascular Channel Formation by Human Melanoma Cells In Vivo and In Vitro: Vasculogenic Mimicry","volume":"155","author":"Maniotis","year":"1999","journal-title":"Am J Pathol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.3390\/ijms18112355","article-title":"Collateral Damage Intended-Cancer-Associated Fibroblasts and Vasculature Are Potential Targets in Cancer Therapy","volume":"18","author":"Cavaco","year":"2017","journal-title":"Int. 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