BICD1 expression, as a potential biomarker for prognosis and predicting response to therapy in patients with glioblastomas
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Shang-Pen Huang1,2,3, Yu-Chan Chang3, Qie Hua Low4, Alexander T.H. Wu5, Chi-Long Chen1,6,7, Yuan-Feng Lin1 and Michael Hsiao3,5,8
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
2Department of Neurology, PoJen General Hospital, Taipei, Taiwan
3Genomics Research Center, Academia Sinica, Taipei, Taiwan
4Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
5The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan
6Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan
7Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan
8Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Michael Hsiao, email: [email protected]
Yuan-Feng Lin, email: [email protected]
KeywordS: BICD1; glioblastoma (GBM); temozolomide (TMZ); biomarker; MGMT
Received: April 07, 2017 Accepted: July 19, 2017 Published: November 27, 2017
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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