Lower expression of Bax predicts poor clinical outcome in patients with glioma after curative resection and radiotherapy/chemotherapy

• Published in: Journal of neuro-oncology Vol. 141; no. 1; pp. 71 - 81
• Main Authors: Wang, Pei-Guo, Li, Yu-Ting, Pan, Yi, Gao, Zhen-Zhu, Guan, Xu-Wen, Jia, Li, Liu, Feng-Ting
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2019; Springer Nature B.V
• Subjects: Apoptosis; BAX protein; bcl-2-Associated X Protein - metabolism; Biomarkers, Tumor - metabolism; Brain Neoplasms - diagnosis; Brain Neoplasms - metabolism; Brain Neoplasms - therapy; Chemotherapy; Clinical outcomes; Combined Modality Therapy; Female; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - metabolism; Glioblastoma - therapy; Glioma; Glioma - diagnosis; Glioma - metabolism; Glioma - therapy; Glioma cells; Humans; Kaplan-Meier Estimate; Laboratory Investigation; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neurology; Oncology; Prognosis; Proteins; Radiation therapy; Statistical analysis; Temozolomide; Treatment Outcome; Bax; Clinical outcome; Glioma; Radiotherapy; And chemotherapy
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-018-03031-9

Background The prognosis in patients with gliomas after surgical resection followed by radiotherapy and/or chemotherapy is still very poor. The pro-apoptotic protein Bax, a short-lived protein in cancers, plays important roles in the sensitivity of glioma cells to spontaneous and therapy-induced apoptosis but and its prognostic value in gliomas is unknown. Methods By an immunohistochemical method, we determined Bax protein expression from 96 patients with gliomas after curative resection. Two statistical analyses were performed to evaluate the prognostic significance of Bax protein: an independent continuous and a multivariate categorical analysis, with test/validation set-defined cut points, and Kaplan–Meier estimated outcome measures of overall survival (OS) and relapse-free survival (RFS). Results Bax protein levels in glioblastoma were significantly decreased compared with grade II gliomas. Lower levels of Bax expression confer worse OS (continuous P  = 0.025; categorical P  = 0.003) and RFS (continuous P  = 0.014; categorical P  < 0.0001) and negatively correlate with the grades of gliomas. Patients underwent radiotherapy followed by surgical resection showed significantly increased OS (median = 45 vs. 17 months) and RFS (median = 39 vs. 16 months). Patients with higher levels of Bax and radiotherapy showed greatly increased survival rates (median OS = 66 months and median RFS = 105 months). Lower expression of Bax also confers inferior clinical outcome for gliomas patients after chemotherapy with temozolomide (OS and RFS P < 0.0001). Conclusion Decreased expression of Bax correlates with poor clinical outcome in patients with gliomas. We propose that Bax protein levels can be used as a reliable prognostic marker for risk-stratify patients with gliomas after curative resection and radiotherapy and/or chemotherapy.