Analysis and Construction of ceRNA Networks Reveal 4 mRNAs as Potential Biomarkers of Temozolomide-resistant Glioblastomas

Abstract Background: Glioblastoma multiform (GBM) is the most malignant tumor of central nervous system. Although temozolomide (TMZ) was reported to improve the prognosis of GBM since applied to clinical practice, its chemoresistance has become a hot research focus and even been thought as the major factor of tumor recurrence. It’s urgent to illustrate the mechanism of TMZ resistance in GBM. Methods: In this study, we retrieved and analyzed expression profiles of TMZ resistant and TMZ sensitive glioma cell lines from GEO datasets, and then identified the enriched pathways of the differentially expressed genes. Moreover, genes involved in the KEGG pathways closely related to GBM from the Comparative Toxicogenomics 2020 Update Database were used for survival analysis of GBM samples from TCGA database. Finally, competing endogenous RNA networks regulating the acquired genes were constructed based on the expression profiles and public database. Results：To our knowledge, we firstly identified 4 mRNAs (LAMA1, COL5A1, ITGA2 and STK11) as potential biomarkers of TMZ resistant GBMs, then constructed their competing endogenous RNA networks. Conclusions: The results would provide theoretical basis for overcoming TMZ chemoresistance and contribute to more optimal chemotherapy of GBMs.