Astrocytoma progression scoring system based on the WHO 2016 criteria

Abstract

Diffuse astrocytoma (including glioblastoma) is morbid with a worse prognosis than other types of glioma. Therefore, we sought to build a progression-associated score to improve malignancy and prognostic predictions for astrocytoma. The astrocytoma progression (AP) score was constructed through bioinformatics analyses of the training cohort (TCGA RNA-seq) and included 18 genes representing distinct aspects of regulation during astrocytoma progression. This classifier could successfully discriminate patients with distinct prognoses in the training and validation (REMBRANDT, GSE16011 and TCGA-GBM Microarray) cohorts (P < 0.05 in all cohorts) and in different clinicopathological subgroups. Distinct patterns of somatic mutations and copy number variation were also observed. The bioinformatics analyses suggested that genes associated with a higher AP score were significantly involved in cancer progression-related biological processes, such as the cell cycle and immune/inflammatory responses, whereas genes associated with a lower AP score were associated with relatively normal nervous system biological processes. The analyses indicated that the AP score was a robust predictor of patient survival, and its ability to predict astrocytoma malignancy was well elucidated. Therefore, this bioinformatics-based scoring system suggested that astrocytoma progression could distinguish patients with different underlying biological processes and clinical outcomes, facilitate more precise tumour grading and possibly shed light on future classification strategies and therapeutics for astrocytoma patients.

Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas

“…Like IDH-mutant lower-grade gliomas, more complex multi-gene and multi-CNV prognostic schemes have also been devised for the IDH-mutant GBM category [65,68,69], and large scale studies have shown that there are multiple genetic and epigenetic phenotypes that can result in longer survival in GBM cohorts [113]. MGMT Promoter methylation predicts improved response to temozolomide [122,123] CCND2 Amplification is correlated with better clinical outcome [115] Total copy number variation (CNV)…”

“…Others have reported a shortened time to malignant progression with increased nuclear immunohistochemical expression of cMYC protein [ 60 ] and worse prognosis with increased nestin immunohistochemistry [ 61 ]. Multiple other specific genetic and immunohistochemical factors have also been considered, including c-MET, EMP3 , GSX2 , EMILIN3 , PPIC , and CHI3L1 [ 62 , 63 , 64 ], and multiple algorithms and multi-gene/multi-CNV panels have been suggested with varying technical complexity, practicality, and prognostic power [ 44 , 49 , 65 , 66 , 67 , 68 , 69 ]. These multi-gene models suggest that in many cases, there are alterations in multiple pathways acting in concert to determine the biologic behavior of the tumor, however, for practical purposes, these panels will likely need to be pared down to key alterations that can be identified soon after the initial histologic diagnosis.…”

“…Like IDH-mutant lower-grade gliomas, more complex multi-gene and multi-CNV prognostic schemes have also been devised for the IDH-mutant GBM category [ 65 , 68 , 69 ], and large scale studies have shown that there are multiple genetic and epigenetic phenotypes that can result in longer survival in GBM cohorts [ 113 ].…”

Open Data for Differential Network Analysis in Glioma

“…Thereby, the latter group is the most aggressive type and to date, non-curable [48,49]. Astrocytoma derive from star-shaped glia cells that are called astrocytes [50]. Glioma cells firstly experience disrupted pathways of cell cycle control, including mutations in p16, CDK-4, cyclin D1 and RB1 [51].…”

Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

“…Conversely, the second group includes those gliomas that are more difficult to treat because of their heterogeneity and invasive growth. These include diffuse astrocytoma (grade II), anaplastic astrocytoma (AA, grade III), and glioblastoma (GBM, grade IV) [1,2]. Depending on the presence or absence of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene mutations, this last group of tumors can be subclassified into IDH-mutant and IDH-wildtype categories, of which the first type is associated with better prognosis [3,4].…”