Year: 2018
Type: article
Study design: Observational Study
Abstract: // Shariq S. Khwaja 1 , Chunyu Cai 2 , Shahed N. Badiyan 3 , Xiaowei Wang 4 and Jiayi Huang 4 1 Department of Neurosurgery, UTHealth McGovern School of Medicine, Mischer Neuroscience Associates, Houston, TX, USA 2 Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA 3 Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA 4 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA Correspondence to: Jiayi Huang, email: [email protected] Keywords: miR-146b; GBM; glioma; recurrence; gene expression profiling Received: March 09, 2017 Accepted: May 16, 2018 Published: June 26, 2018 ABSTRACT Background: Glioblastoma (GBM) has a high rate of local recurrence despite chemoradiotherapy (CRT). Genome-wide expression profiling was performed on patient tumors before and after chemoradiotherapy to identify genes and gene pathways associated with recurrence. Results: Median time to recurrence was 8.9 months with median time to second surgery of 9.6 months. The microRNA (miRNA) analysis identified 9 oncologic and immune-related miRNAs to be differentially expressed, including the hypoxia-related miR-210 and the immune-modulatory miR-146b. More than 1200 differentially-expressed genes were identified with RNA-sequencing (RNA-seq). Gene set enrichment analysis (GSEA) identified p53 signaling, Notch, Wnt, VEGF, and MEK gene sets enriched in recurrent GBM. Consistent with the miRNA profiling data, the miR-146b target gene set from GSEA analysis was also associated with recurrence. Methods: Fourteen patients with GBM recurrence after CRT who had available tumor tissue from the initial diagnosis as well as recurrence were selected. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tumor specimens. Genome-wide expression profiling using RT-PCR for miRNA analysis and RNA-seq for messenger RNA (mRNA) analysis were conducted to identify differentially-expressed genes. GSEA was performed on the differential expression data. Conclusions: Genome-wide expression profiling identifies multiple oncologic and immune-related gene sets associated with GBM recurrence. In particular, immune-related miR-146b is upregulated in recurrence and deserves further investigation.
Source: Oncotarget
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: G242792408, G9000065691
OpenAlex ID: W2811049000