Chemotherapy sensitivity of primary glioblastoma cells and immunohistochemical markers to predict of survival of patients with of glioblastoma.

Abstract

Purpose: To evaluate the IDH1, p53 protein (TP53), epidermal growth factor receptor (EGFR), Ki-67 nuclear antigen, ATP-dependent helicase (ATRX), glial fibrillary acid protein (GFAP), methylated DNA-protein cysteine methyltransferase (MGMT), podoplanin (PDPN), transferrin (TR) in glioblastoma multiforme (GBM) samples. In addition, we investigated whether the expression of protein markers and the response to chemotherapy in vitro are associated with lifespan in patients with GBM.

Methods: Thirty patients diagnosed with GBM were immunohistochemically (IHC) evaluated for IDH1, TP53, EGFR, Ki-67, GFAP, MGMT, ATRX, PDPN, and TR. The sensitivities of primary GBM cells to chemotherapy temozolomide (TMZ), doxorubicin (DOX), carboplatin (CARB), cisplatin (CIS), and etoposide (ETO) were analyzed by measuring cell viability with the MTT assay. Kaplan-Meier survival analysis was performed using GraphPad Prism software.

Results: In this study, we found significant associations between DOX (500 μM, p = 0.0446), CARB (3000 μM, p = 0.0015) and CIS (1800 μM, p = 0.0293) with increased lifespan of GBM patients. An association between a combination of Ki-67 expression (>20%) and CARB (3000 μM, p = 0.016) with prolonged lifespan of GBM patients was shown. A relationship between Ki-67, ETO (12 μM, p = 0.0032), and an increase lifespan (13.5 vs. 6 months) in GBM patients was detected. A combination of ATRX (<60%) and CIS correlated with an increased lifespan for GBM patients (12.5 vs. 4 months, respectively, p < 0.05). Combinations of DOX (500 μM) and GFAP (<60%) were associated with prolonged lifespan for patients (p = 0.047).

Conclusions: The results of the current study suggest that the expressions of IHC markers in combination with the response to chemotherapy for GBM cells may be a good predictor of lifespan patient. Hence, GBM can be grouped into prognostically relevant subgroups using these IHC markers expression signatures individually, as well as the combined with chemotherapy. In vivo drug testing on primary GBM cells in combination with expression of marker proteins can predict tumor response to personalized therapy and lifespan of the patients.