Over‐expression of BICD1 gene as a marker for clinically predicting Temozolomide resistance in Glioblastomas

Abstract

Glioblastoma multiforme (GBM) is a highly malignant tumor with a median survival of only 14 months, for which surgical resection, radiotherapy, and chemotherapy are the major clinical treatments. Temozolomide (TMZ) is currently the only FDA approved effective chemotherapy drug for treatment of GBM; however, cancer cells often develop drug resistance after TMZ treatment and eventually lead to treatment failure. Here, we demonstrated that Bicaudal D Homolog 1 (BICD1) gene would be a potential biomarker for predicting TMZ resistance in GBM patients. In our study, we found that T98G GBM cell is highly resistant to TMZ (IC50>200μM), while U87 GBM cell is highly sensitive to TMZ (IC50<100μM) by MTT assay. After treated with TMZ, gene expression of BICD1 was significantly upregulated in T98G cells and downregulated in U87. The available clinical datasets of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) indicated that over‐expression of BICD1 correlates with a poor outcome of GBM patients. Moreover, the TMZ sensitivity was recruited in T98G and SF126 GBM cells after their BICD1 genes were knocked down. Thus, over‐expression of BICD1 plays an important role in TMZ resistance when treating GBM.