Abstract
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.
Highlights
Glioblastoma is a disease with a notably poor prognosis, with a 2‐year prognosis is as low as 27% in Europe and in the United States [1,2]
Patients had been treated with radiotherapy plus concomitant and maintenance temozolomide chemotherapy following maximal safe resection of the tumor
Patients had an improved preoperative and postoperative Karnofsky performance status (KPS) score in group B compared with patients in group A, but the KPS scores did not differ significantly
Summary
Glioblastoma is a disease with a notably poor prognosis, with a 2‐year prognosis is as low as 27% in Europe and in the United States [1,2]. Patients undergo concurrent chemoradiation following tumor resection, and chemotherapy, namely alkylating agent temozolomide, is administered as monotherapy. Despite the changes in treatment protocols in the past decade and the extensive research in the field of glioblastoma treatment options, the majority of patients succumb 16‐24 months after diagnosis [1,2,3,4]. Specific clinical factors affect patient outcome, including sex, age, Karnofsky performance status (KPS) score and tumor size, but these are poor predictors of prognosis and cannot be used successfully in everyday clinical practice [5,6]. Maximum safe resection may improve patient survival; neither the minimal cut‐off resection volume nor the maximum residual tumor volume that is associated with survival benefit has been established [7]
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