Oncotarget

Research Papers:

The immune-related microRNA miR-146b is upregulated in glioblastoma recurrence

Shariq S. Khwaja, Chunyu Cai, Shahed N. Badiyan, Xiaowei Wang and Jiayi Huang _

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Oncotarget. 2018; 9:29036-29046. https://doi.org/10.18632/oncotarget.25528

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Abstract

Shariq S. Khwaja1, Chunyu Cai2, Shahed N. Badiyan3, Xiaowei Wang4 and Jiayi Huang4

1Department of Neurosurgery, UTHealth McGovern School of Medicine, Mischer Neuroscience Associates, Houston, TX, USA

2Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA

3Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA

4Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA

Correspondence to:

Jiayi Huang, email: jiayi.huang@wustl.edu

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.


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