Virga József, Bognár László, Hortobágyi Tibor, Zahuczky Gábor, Csősz Éva, Kalló Gergő, Tóth Judit, Hutóczki Gábor, Reményi-Puskár Judit, Steiner László, Klekner Almos
Department of Neurosurgery, University of Debrecen Clinical Center, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
Department of Pathology, University of Debrecen Clinical Center, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
Pathol Oncol Res. 2018 Jan;24(1):35-43. doi: 10.1007/s12253-017-0194-6. Epub 2017 Feb 4.
Peritumoral infiltration is characteristic of astrocytomas even in low-grade tumors. Tumor cells migrate to neighbouring tissue and cause recurrence. The extracellular matrix (ECM) plays a role in tumor invasion; expression levels of its components' have been linked to tumor invasion. This study determines the mRNA and protein expression of 20 invasion-related ECM components by examining non-tumor brain; grade I-II-III astrocytoma and glioblastoma samples. Expression levels were measured by QRT-PCR and mass-spectroscopy. The connection between the expression pattern and tumor grade is statistically analyzed. During the analysis of data, key molecules (brevican, cadherin-12, fibronectin and integrin-β1) correlating the most with tumor grade were selected. While the mRNA level of brevican, ErbB2, fibronectin, integrin-β1 and versican discriminates low-grade from high-grade gliomas, of proteins RHAMM, integrin-α1 and MMP2 seems important. The expression pattern was found to be distinctive for tumor grade, as statistical classifiers are capable of identifying an unknown sample's grade using them. Furthermore, normal brain and glioma expression patterns, along with low-grade astrocytoma and glioblastoma samples, differ the most. Determining the invasion-related molecules' expression profile provides extra information regarding the tumor's clinical behavior. Additionally, identifying molecules playing a key role in glioma invasion could uncover potential therapeutic targets in the future.
瘤周浸润是星形细胞瘤的特征,即使在低级别肿瘤中也是如此。肿瘤细胞迁移至邻近组织并导致复发。细胞外基质(ECM)在肿瘤侵袭中起作用;其成分的表达水平与肿瘤侵袭有关。本研究通过检测非肿瘤脑组织、I-II-III级星形细胞瘤和胶质母细胞瘤样本,确定20种与侵袭相关的ECM成分的mRNA和蛋白质表达。通过定量逆转录聚合酶链反应(QRT-PCR)和质谱法测量表达水平。对表达模式与肿瘤分级之间的联系进行统计学分析。在数据分析过程中,选择了与肿瘤分级相关性最高的关键分子(短蛋白聚糖、钙黏蛋白-12、纤连蛋白和整合素-β1)。虽然短蛋白聚糖、表皮生长因子受体2(ErbB2)、纤连蛋白、整合素-β1和多功能蛋白聚糖的mRNA水平可区分低级别和高级别胶质瘤,但就蛋白质而言,透明质酸介导的运动受体(RHAMM)、整合素-α1和基质金属蛋白酶2(MMP2)似乎很重要。发现表达模式因肿瘤分级而异,因为统计分类器能够使用它们识别未知样本的分级。此外,正常脑组织和胶质瘤的表达模式,以及低级别星形细胞瘤和胶质母细胞瘤样本之间差异最大。确定与侵袭相关分子的表达谱可提供有关肿瘤临床行为的额外信息。此外,识别在胶质瘤侵袭中起关键作用的分子可能在未来揭示潜在的治疗靶点。