1 Citation (Scopus)

Abstract

There is variation in the survival and therapeutic outcome of patients with glioblastomas (GBMs). Therapy resistance is an important challenge in the treatment of GBM patients. The aim of this study was to identify Temozolomide (TMZ) related genes and confirm their clinical relevance. The TMZ-related genes were discovered by analysis of the gene-expression profiling in our cell-based microarray. Their clinical relevance was verified by in silico meta-analysis of the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Our results demonstrated that BICD1 expression could predict both prognosis and response to therapy in GBM patients. First, high BICD1 expression was correlated with poor prognosis in the TCGA GBM cohort (n=523) and in the CGGA glioma cohort (n=220). Second, high BICD1 expression predicted poor outcome in patients with TMZ treatment (n=301) and radiation therapy (n=405). Third, multivariable Cox regression analysis confirmed BICD1 expression as an independent factor affecting the prognosis and therapeutic response of TMZ and radiation in GBM patients. Additionally, age, MGMT and BICD1 expression were combinedly utilized to stratify GBM patients into more distinct risk groups, which may provide better outcome assessment. Finally, we observed a strong correlation between BICD1 expression and epithelial-mesenchymal transition (EMT) in GBMs, and proposed a possible mechanism of BICD1-associated survival or therapeutic resistance in GBMs accordingly. In conclusion, our study suggests that high BICD1 expression may result in worse prognosis and could be a predictor of poor response to TMZ and radiation therapies in GBM patients.

Original languageEnglish
Pages (from-to)113766-113791
Number of pages26
JournalOncotarget
Volume8
Issue number69
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

temozolomide
Glioblastoma
Biomarkers
Atlases
Glioma
Genome
Therapeutics
Radiotherapy
Epithelial-Mesenchymal Transition
Survival
Gene Expression Profiling
Computer Simulation
Genes
Meta-Analysis
Neoplasms
Regression Analysis
Outcome Assessment (Health Care)
Radiation

Keywords

  • BICD1
  • Biomarker
  • Glioblastoma (GBM)
  • MGMT
  • Temozolomide (TMZ)

ASJC Scopus subject areas

  • Oncology

Cite this

BICD1 expression, as a potential biomarker for prognosis and predicting response to therapy in patients with glioblastomas. / Huang, Shang Pen; Chang, Yu Chan; Low, Qie Hua; Wu, Alexander T.H.; Chen, Chi Long; Lin, Yuan Feng; Hsiao, Michael.

In: Oncotarget, Vol. 8, No. 69, 01.01.2017, p. 113766-113791.

Research output: Contribution to journalArticle

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abstract = "There is variation in the survival and therapeutic outcome of patients with glioblastomas (GBMs). Therapy resistance is an important challenge in the treatment of GBM patients. The aim of this study was to identify Temozolomide (TMZ) related genes and confirm their clinical relevance. The TMZ-related genes were discovered by analysis of the gene-expression profiling in our cell-based microarray. Their clinical relevance was verified by in silico meta-analysis of the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Our results demonstrated that BICD1 expression could predict both prognosis and response to therapy in GBM patients. First, high BICD1 expression was correlated with poor prognosis in the TCGA GBM cohort (n=523) and in the CGGA glioma cohort (n=220). Second, high BICD1 expression predicted poor outcome in patients with TMZ treatment (n=301) and radiation therapy (n=405). Third, multivariable Cox regression analysis confirmed BICD1 expression as an independent factor affecting the prognosis and therapeutic response of TMZ and radiation in GBM patients. Additionally, age, MGMT and BICD1 expression were combinedly utilized to stratify GBM patients into more distinct risk groups, which may provide better outcome assessment. Finally, we observed a strong correlation between BICD1 expression and epithelial-mesenchymal transition (EMT) in GBMs, and proposed a possible mechanism of BICD1-associated survival or therapeutic resistance in GBMs accordingly. In conclusion, our study suggests that high BICD1 expression may result in worse prognosis and could be a predictor of poor response to TMZ and radiation therapies in GBM patients.",
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AU - Lin, Yuan Feng

AU - Hsiao, Michael

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