Screening and Authentication of Key Genes and Prognostic Value Analysis in Oligodendroglial Tumors

Background: Emerging evidence indicates that various functional genes with altered expression are involved in the human tumor progression. This study is aimed at identifying novel key genes that may be used for oligodendroglial tumor diagnosis, prognosis, and targeted therapy. Methods: This study included three expression profiles (GSE15824, GSE29796 and GSE108474) obtained from the Gene Expression Omnibus (GEO). GEO2R was used to analyze the differentially expressed genes (DEGs) between normal samples and oligodendroglial tumor, including oligodendroglioma and anaplastic oligodendroglioma. The functional and pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the identified DEGs was constructed using the Search Tool for the Retrieval of Interacting Gene, and hub genes were identified. ONCOMINE and The Cancer Genome Atlas (TCGA) databases were used to verify the expression of the hub genes in oligodendroglial tumor tissues and the hub genes on the overall survival of oligodendroglial tumor patients. Results: A total of 128 DEGs were identified from the three expression profiles. These DEGs were enriched with functional processes and pathways related to oligodendroglial tumor pathogenesis. From the PPI network, five hub genes were identified. The expression of the five hub genes was all upregulated in oligodendroglial tumor tissues compared with the control tissues. Kaplan-Meier survival curves indicated that high expression of cullin 3 (CUL3), cop9 signalosome subunit 8 (COPS8), cullin associated and neddylation dissociated 1 (CAND1), F-box protein 22 (FBXO22), and leucine rich repeat containing 41 (LRRC41) predicted poor overall survival in oligodendroglial tumor patients (all log-rank P < 0.01). Conclusions: These results revealed that the DEGs may serve as candidate key genes during oligodendroglial tumor pathogenesis. The five hub genes, including CUL3, COPS8, CAND1, FBXO22, and LRRC41, may serve as promising prognostic biomarkers in oligodendroglial tumor.

Cognitive and brain structural changes in long-term oligodendroglial tumor survivors

Background We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with chemotherapy (CT) (79%). Methods Oligodendroglial tumor patients (based on the World Health Organization [WHO] 2007 classification) who completed RT ± CT at least 2 years before the study initiation, were classified into 3 groups according to the time treatment was completed: Group 1 = 2–5 years (n = 22), Group 2 = 6–10 years (n = 13), and Group 3 >10 years (n = 13). All patients had a cross-sectional neuropsychological evaluation (n = 48) and a longitudinal volumetric analysis (gray matter [GM; n = 34]) between postsurgical and last follow-up MRI. White matter (WM) changes on MRI were assessed using a qualitative scale. Results There were no differences regarding tumor or treatment-related characteristics between groups. Six of 22 patients (27.3%) in Group 1; 5/13 (38.5%) in Group 2; and 9/13 (69.2%) in Group 3 had cognitive impairment that was considered severe in 3/22 patients (13.6%) in Group 1; 4/13 (30.8%) in Group 2; and 6/13 (46.2%) in Group 3. Patients in Groups 2 and 3 showed significant GM atrophy and more leukoencephalopathy than Group 1. Cognitive deficits were associated with brain atrophy and WM changes. Conclusions Long-term oligodendroglial tumor survivors who underwent standard RT ± CT treatment, mainly >5 years of its completion, present cognitive impairment, especially on memory and executive functions, associated with late GM and WM damage, thus highlighting the need of developing future strategies in patients with oligodendroglial tumor and long expected survival.

Radiomics method to predict loss of heterozygosity on chromosome 1p/19q of oligodendroglial tumor.

2043 Background: Oligodendroglial tumor (OT) is one of the main types of gliomas, which is incurable in current situation. As a tumor-specific genetic alteration of OTs, loss of heterozygosity (LOH) on chromosome 1p/19q indicates a preferable response to chemo/radiotherapy and a better survial, which could be used as a key molecular signature for personalized treatment decision making. However, 1p/19q LOH status is now commonly obtained by fluorescence in situ hybridization after the tumor resection, which is highly likely to lead functin deficit with tumor locating on eloquent area. Thus, a noninvasive predicition on 1p/19q LOH is required. Here, we used a "Radiomics" method to achieve the prediction based on magnetic resonance imaging in this study. Methods: A cohort of 113 OT patients was collected from Beijing Tiantan Hospital. 593 three-dimensional imaging features were extracted on T2-weighted images including textural and non-textural features. We used "minimum redundancy maximum relevance" and "iterative backward elemination and forward inclusion" algorithms to pick up the most effective features with a p-value < 0.05. With the selected features as the input, support vector machine algorithm was adopted to predict the 1p/19q LOH status with 10-fold cross validation. Comparisons were made between the traditional clinical predictors and the established model. Results: The prediction accuracy for 1p/19q LOH turned out to be 86.6%. The top three features contributing most to the prediction were respectively: GlobalUniformity, GaborBankD4GLRLMLGRE and GaborBankD4GLRLMSRLGE. The predictive performance of the radiomics model was proved to be far more valid than the clinical predictors (indistict tumor border and heterogeneous signal intensity) with the higher area under curve (AUC). Compared with the best single feature (GlobalUniformity, AUC: 0.749), this combined-feature model has the best diagnostic performance with an AUC of 0.898. Conclusions: This study reveals the intrinsic association between the imaging features and 1p/19q LOH status, meanwhile, realizes the high precision prediction, providing reliable basis for the pre-operative treatment regime.