Abstract
Abstract Glioblastoma (GBM) is the most common and aggressive form of primary brain tumor. Due to its extremely malignant and invasive nature, the mean survival period of GBM patients is only 12-15 months from diagnosis. GBM patients rely on current treatment options, including surgery, radiation and chemotherapy (temozolomide). However, these treatment options fail to improve quality of patients' lives. After the treatment of temozolomide (TMZ) chemotherapy, more than 80% of the GBM tumors relapse. One of the most significant issues with the standard treatment strategy is that these secondary tumors have usually developed a chemoresistance to TMZ. This indicates that the secondary tumors have different tumor characteristics than primary tumors. Our goal is to examine the TMZ-treated and non-treated tumors in order to investigate the lipid expression changes in GBM samples by shotgun lipidomics. Lipids are known to play a critical role in cancer cell initiation and progression governed by oncogenic signaling pathways. Our previous study showed that more than 90% of identified lipids from orthotopic GBM tumors were significantly under-expressed compared to the control samples, which suggests that studying changes of lipids in tumor environment might help us better develop better strategies to overcome chemoresistance. We hypothesize that temozolomide promotes tumor heterogeneity and a mutagenic microenvironment in GBM, and lipid profiles of GBM can be a potential key biomarker for chemoresistance and cancer development. Our study focuses on investigating changes in lipid expression between TMZ-treated and non-treated GBM tumors by shotgun lipidomics. Intracerebral implants of the GBM10 cell line were performed in the right cerebral hemisphere in NOD/SCID/gchainnull mice obtained from the In Vivo Therapeutics Core Indiana University School of Medicine (IUSCC/IUSM). Ten mice received three rounds of TMZ treatment, and ten mice received no treatment. Tumors were harvested approximately 25 days after the implants and stored in -80C immediately. We plan to investigate lipid biomarkers of GBM by utilizing shotgun lipidomics to examine changes in the tumor lipid composition as a result of temozolomide treatment. In order to visualize the data, our group will utilize supervised statistical analysis methods (principal component analysis - PCA), univariate statistics and receiver operating characteristics (ROC) curve to show the differences of lipid profiles and define prospective biomarkers. Our findings could contribute to the development or the monitoring of therapeutic intervention strategies for tumors that recur after standard care of treatment in glioblastoma. Citation Format: Soo Jung Ha, Lauren Bailey, Christina Ferreira, Haiyan Wang, Barbara Bailey, Jixin Ding, M Reza Saadatzadeh, Karen E. Pollok, Kari Clase. Shotgun lipidomics analysis of temozolomide-treated glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A26.
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