Prognostic and Clinical Values of Chaperone Protein P4HB in Malignant Glioma

Abstract Introduction. Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified by our group to play important roles in association with glioma malignancy and temozolomide (TMZ) resistance through the unfolded protein response (UPR). The present study focused on the prognostic value of P4HB in glioma. Methods. P4HB expression was assessed by immunohistochemical staining and semi-quantified by pathologist visual scoring in 73 WHO grade I-IV gliomas. Results were correlated with clinicopathological data. Results. Our results show that P4HB expression was significantly associated several clinicopathological parameters including age (p=0.035), tumour grade (p=0.002), and the number of TMZ treatment cycles received (p=0.043). Using Kaplan-Meier analysis, P4HB expression was positively correlated with mortality (p=0.014) and disease progression (p=0.026). In patients treated with TMZ, high P4HB expression level was significantly associated with poorer overall survival (OS) (p=0.014) and progression free survival (PFS) (p=0.027). The association between MGMT promoter methylation and P4HB expression was also interrogated. Patients with MGMTMethP4HBLow tumours had the most favourable progression free survival (48 months) than patients with other combination of MGMT methylation status and P4HB expression (log rank p=0.001). Multivariate analysis revealed that P4HB was an independent prognostic indicator for OS (p=0.048). Conclusions. P4HB could constitute an independent prognostic marker, especially for high grade glioma with the potential for informing a nuanced pathological stratification during clinical decision-making with respect to MGMT promoter methylation status and TMZ treatment.