Virga József, Szivos László, Hortobágyi Tibor, Chalsaraei Mahan Kouhsari, Zahuczky Gábor, Steiner László, Tóth Judit, Reményi-Puskár Judit, Bognár László, Klekner Almos
Department of Neurosurgery, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neuropathology, Institute of Pathology, University of Debrecen, H-4032 Debrecen, Hungary.
Oncol Lett. 2019 Jan;17(1):797-806. doi: 10.3892/ol.2018.9649. Epub 2018 Oct 31.
Glioblastoma is the most common malignant central nervous system tumor. Patient outcome remains poor despite the development of therapy and increased understanding of the disease in the past decades. Glioma cells invade the peritumoral brain, which results in inevitable tumor recurrence. Previous studies have demonstrated that the extracellular matrix (ECM) is altered in gliomas and serves a major role in glioma invasion. The present study focuses on differences in the ECM composition of tumors in patients with poor and improved prognosis. The mRNA and protein expression of 16 invasion-associated ECM molecules was determined using reverse trascription-quantitiative polymerase chain reaction and immunohistochemistry, respectively. Clinical factors of patients with different prognoses was also analyzed. It was determined that age and postoperative Karnofsky performance score were associated with patient survival. Furthermore, Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR3), murine double minute 2 (MDM2) and matrix metallopeptidase 2 (MMP2) mRNA levels were significantly different between the two prognostic groups. Additionally, brevican, cluster of differentiation 44, hyaluronan mediated motility receptor, integrin-αV and -β1, and MDM2 protein expression were indicated to be significantly different in immunohistochemistry slides. Using the expression profile, including the invasion spectrum of the samples, it was possible to identify the prognostic group of the sample with high efficacy, particularly in cases with poor prognosis. In conclusion, it was determined that ECM components exhibit different expression levels in tumors with different prognoses and thus the invasion spectrum can be used as a prognostic factor in glioblastoma.
胶质母细胞瘤是最常见的恶性中枢神经系统肿瘤。尽管在过去几十年中治疗方法有所发展且对该疾病的了解有所增加,但患者的预后仍然很差。胶质瘤细胞侵袭瘤周脑组织,这导致肿瘤不可避免地复发。先前的研究表明,细胞外基质(ECM)在胶质瘤中发生改变,并在胶质瘤侵袭中起主要作用。本研究聚焦于预后不良和预后改善患者肿瘤的ECM组成差异。分别使用逆转录-定量聚合酶链反应和免疫组织化学法测定了16种与侵袭相关的ECM分子的mRNA和蛋白表达。还分析了不同预后患者的临床因素。结果确定年龄和术后卡诺夫斯基表现评分与患者生存相关。此外,两个预后组之间Fms相关酪氨酸激酶4/血管内皮生长因子受体3(FLT4/VEGFR3)、鼠双微体2(MDM2)和基质金属肽酶2(MMP2)的mRNA水平存在显著差异。此外,免疫组织化学切片显示短蛋白聚糖、分化簇44、透明质酸介导的运动受体、整合素-αV和-β1以及MDM2蛋白表达存在显著差异。利用包括样本侵袭谱在内的表达谱,可以高效识别样本的预后组,尤其是在预后不良的病例中。总之,确定ECM成分在不同预后的肿瘤中表现出不同的表达水平,因此侵袭谱可作为胶质母细胞瘤的一个预后因素。