PARP14 correlates with GBM proliferation and poor prognosis by elevating expression of SAMD/SAMD9L.

Abstract

Glioblastoma(GBM) is the most common primary tumor of the central nervous system with an extremely dismal prognosis. Many progresses have been made such as the discovery of new molecular biomarkers and target drugs especially IDH inhibitors. However, GBM prognosis is still poor, which requires more biomarkers and drug targets for more precision classification and treatment. Potential prognostic biomarkers of GBM were screened by TCGA database, and ectopic up-regulation of PARP14 was identified. Expression and clinical significance of PARP14 were detected in our GBM cohort consisting of 143 patients with gross total surgical resection. Related genes with PARP14 were further screened and identified by in silico analysis and in vitro experiments. The expression and prognostic significance of SAMD9 and SAMD9L were verified with IHC and survival analysis in our cohort. PARP14 was up-regulated in GBM compared with non-tumor adjacent tissues. PARP14 correlated with poor prognosis and can be regarded as an independent prognostic biomarker of GBM. PARP14 expression was positively associated with SAMD9 and SAMD9L in GBM. In GBM cells, PARP14 could increase the expression of SAMD9 and SAMD9L. SAMD9 and SAMD9L were highly expressed in high-PARP14 subset and were both prognostic biomarkers of GBM. Moreover, PARP14 increased GBM proliferation by inducing SAMD9 and SAMD9L expression. PARP14, SAMD9, and SAMD9L are prognostic biomarkers of GBM predicting poor prognosis. PARP14 promotes GBM cell proliferation by inducing SAMD9 and SAMD9L expression. Our results indicate that PARP14/SAMD9/SAMD9L are prognostic biomarkers and potential drug targets of GBM.