Identification of biomarkers for pseudo and true progression of GBM based on radiogenomics study
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Xiaohua Qian1,*, Hua Tan1,*, Jian Zhang1, Keqin Liu1, Tielin Yang2, Maode Wang3, Waldemar Debinskie4, Weilin Zhao1, Michael D. Chan4, Xiaobo Zhou1
1Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
2School of Life Science, Xi’an Jiaotong University, Xi’an, Shanxi 710049, China
3The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shanxi 710061, China
4Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
*These authors have contributed equally to this work
Xiaobo Zhou, email: [email protected]
Keywords: GBM, pseudo and true tumor progression, radiogenomics, IRF9, XRCC1
Received: January 19, 2016 Accepted: May 05, 2016 Published: July 13, 2016
The diagnosis for pseudoprogression (PsP) and true tumor progression (TTP) of GBM is a challenging task in clinical practices. The purpose of this study is to identify potential genetic biomarkers associated with PsP and TTP based on the clinical records, longitudinal imaging features, and genomics data. We are the first to introduce the radiogenomics approach to identify candidate genes for PsP and TTP of GBM. Specifically, a novel longitudinal sparse regression model was developed to construct the relationship between gene expression and imaging features. The imaging features were extracted from tumors along the longitudinal MRI and provided diagnostic information of PsP and TTP. The 33 candidate genes were selected based on their association with the imaging features, reflecting their relation with the development of PsP and TTP. We then conducted biological relevance analysis for 33 candidate genes to identify the potential biomarkers, i.e., Interferon regulatory factor (IRF9) and X-ray repair cross-complementing gene (XRCC1), which were involved in the cancer suppression and prevention, respectively. The IRF9 and XRCC1 were further independently validated in the TCGA data. Our results provided the first substantial evidence that IRF9 and XRCC1 can serve as the potential biomarkers for the development of PsP and TTP.
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