Glioblastoma gene expression subtypes and correlation with clinical, molecular and immunohistochemical characteristics in a homogenously treated cohort: GLIOCAT project.

Abstract

2029 Background: Glioblastoma (GBM) gene expression subtypes have been described in last years, data in homogeneously treated patients is lacking. Methods: Clinical, molecular and immunohistochemistry (IHC) analysis from patients with newly diagnosed GBM homogeneously treated with standard radiochemotherapy were studied. Samples were classified based on the expression profiles into three different subtypes (classical, mesenchymal, proneural) using Support Vector Machine (SVM), the K-nearest neighbor (K-NN) and the single sample Gene Set Enrichment Analysis (ssGSEA) classification algorithms provided by GlioVis web application. Results: GLIOCAT Project recruited 432 patients from 6 catalan institutions, all of whom received standard first-line treatment (2004 -2015). Best paraffin tissue samples were selected for RNAseq and reliable data were obtained from 124. 82 cases (66%) were classified into the same subtype by all three classification algorithms. SVM and ssGEA algorithms obtain more similar results (87%). No differences in clinical variables were found between the 3 GBM subtypes. Proneural subtype was enriched with IDH1 mutated and G-CIMP positive tumors. Mesenchymal subtype (SVM) was enriched in unmethylated MGMT tumors (p = 0.008), and classical (SVM) in methylated MGMT tumors (p = 0.008). Long survivors ( > 30 months) were rarely classified as mesenchymal (0-7.5%) and were more frequently classified as Proneural (23.1-26.). Clinical (age, resection, KPS) and molecular ( IDH1, MGMT) known prognostic factors were confirmed in this serie. Overall, no differences in prognosis were observed between 3 subtypes, but a trend to worse survival in mesenchymal was observed in K-NN (9.6 vs 15 ). Mesenchymal subtype presented less expression of Olig2 (p < 0.001) and SOX2 (p = 0.003) by IHC, but more YLK-40 expression (p = 0.023, SVM). On the other hand, classical subtype expressed more Nestin (p = 0.004) compared to the other subtypes (K-NN). Conclusions: In our study we have not found correlation between glioblastoma expression subtype and outcome. This large serie provides reproducible data regarding clinical-molecular-immunohistochemistry features of glioblastoma genetic subtypes.

Lack of benefit of temozolomide for MGMT methylated patients with high vascular glioblastoma: a confirmatory study

“…To achieve our main purposes, we used an independent and major multicenter cohort of 123 glioblastoma patients. Our results validate the hypothesis proposed in [48], since we have found significant associations (p<0.05) between MGMT methylation status and patient survival only for the moderate vascular group of patients, but not for the high vascular group (p>0.05). This is, prognosis of patients with a moderate vascular tumor will be affected by MGMT methylation status, while survival times for the high vascular group do not differ, independently of the MGMT methylation status.…”

“…For this study, 123 glioblastoma patients were included from the GLIOCAT database [48], which includes patients from the following 6 centers from Cataluña, Spain: (I) Instituto Catalán de Oncología (ICO) de Badalona (Barcelona), (II) Hospital del Mar (Barcelona), (III) Hospital Clínic (Barcelona), (IV) ICO Hospitalet (Barcelona), (V) ICO Girona (Girona) and, (VI) Hospital Sant Pau (Barcelona).…”

Characterization of vascular heterogeneity of astrocytomas grade 4 for supporting patient prognosis estimation, and treatment response assessment

“…To achieve our main purposes, we used an independent and major multicenter cohort of 123 glioblastoma patients. Our results validate the hypothesis proposed in 208 , since we have found significant associations (p < 0.05) between MGMT methylation status and patient survival only for the moderate vascular group of patients, but not for the high vascular group (p > 0.05). This is, prognosis of patients with a moderate vascular tumor will be affected by MGMT methylation status, while survival times for the high vascular group do not differ, independently of the MGMT methylation status.…”

“…For this study, 123 glioblastoma patients were included from the GLIOCAT database 208 , which includes patients from the following six centers from Cataluña, Patients still alive at readout were considered censored observations. The date of censorship was the last date of contact with the patient or, if not available, the date of the last MRI exam.…”

Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated MGMT

“…For this study, 123 glioblastoma patients were included from the GLIOCAT database [48], which includes patients from the following six centers from Cataluña, Spain: (I) Instituto Catalán de Oncología (ICO) de Badalona (Barcelona), (II) Hospital del Mar (Barcelona), (III) Hospital Clínic (Barcelona), (IV) ICO Hospitalet (Barcelona), (V) ICO Girona (Girona), and (VI) Hospital Sant Pau (Barcelona). A Material Transfer Agreement was approved by all the participating centers and an acceptance report was issued by the Ethical Committee of each center.…”