School of Medicine, Shandong University, Jinan, China.
Department of Pathology, Anhui Provincial Hospital, Shandong University, Hefei, China.
Pathol Oncol Res. 2021 Aug 18;27:1609844. doi: 10.3389/pore.2021.1609844. eCollection 2021.
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 ( < 0.001, = 0.040, and = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor ( < 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 ( < 0.001 and < 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (r = 0.435, < 0.001 and r = 0.317, < 0.001). Besides, Hypoxia-inducible factor-1α (HIF1α) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe ( = 0.010 and = 0.029). However, no obvious connection was detected between HIF1α expression and VM formation ( = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients ( < 0.001, HR = 7.928, 95%CI: 3.382-18.584, and = 0.007, HR = 4.534, 95%CI: 1.504-13.675, 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.
血管生成拟态 (VM) 已被确定为恶性肿瘤中一种重要的血管生成机制,但在少突胶质细胞瘤中,其临床意义和机制知之甚少。在这项研究中,在 136 例少突胶质细胞瘤样本中检测到 28 例 (20.6%) VM 阳性病例,VM 阳性与更高的世界卫生组织 (WHO) 分级、更低的卡氏功能状态 (KPS) 评分和复发性肿瘤显著相关 ( < 0.001、 = 0.040 和 = 0.020)。与 VM 阴性肿瘤患者相比,VM 阳性少突胶质细胞瘤患者的无进展生存期 (PFS) 更短 ( < 0.001),但这些患者的总生存期 (OS) 无显著差异。在 136 例少突胶质细胞瘤样本中,分别有 31 例 (22.8%) 和 34 例 (25.0%)检测到磷酸化丝氨酸/苏氨酸激酶共济失调毛细血管扩张突变 (pATM) 和磷酸化共济失调毛细血管扩张和 Rad3 相关 (pATR) 水平升高。较高的 pATM 和 pATR 表达均与较短的 PFS 相关 ( < 0.001 和 < 0.001)。VM 阳性少突胶质细胞瘤标本的 pATM 和 pATR 染色倾向于高于 VM 阴性标本 (r = 0.435, < 0.001 和 r = 0.317, < 0.001)。此外,在 14 例 (10.3%) 样本中检测到缺氧诱导因子-1α (HIF1α) 表达,与更高的 WHO 分级和非额叶 ( = 0.010 和 = 0.029) 相关。然而,HIF1α 表达与 VM 形成之间没有明显的联系 ( = 0.537)。最后,单因素或多因素分析均表明,VM 是少突胶质细胞瘤患者的独立不良预后因素 ( < 0.001,HR = 7.928,95%CI:3.382-18.584,和 = 0.007,HR = 4.534,95%CI:1.504-13.675)。VM 是少突胶质细胞瘤患者肿瘤进展的潜在预后标志物。与治疗耐药相关的 ATM 和 ATR 的磷酸化可能与 VM 形成有关。VM 在肿瘤进展中的作用以及 pATM/pATR 在 VM 形成中的作用可能为少突胶质细胞瘤的治疗提供潜在的治疗靶点。