Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Centre for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
The Graduate School, Tianjin Medical University, Tianjin, 300070, China.
J Neurooncol. 2019 Jan;141(1):71-81. doi: 10.1007/s11060-018-03031-9. Epub 2018 Nov 16.
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.
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).
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).
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.
在手术切除后接受放疗和/或化疗的胶质瘤患者的预后仍然非常差。促凋亡蛋白 Bax 是癌症中的一种短寿命蛋白，在胶质瘤细胞对自发性和治疗诱导的细胞凋亡的敏感性中发挥重要作用，但 Bax 在胶质瘤中的预后价值尚不清楚。
通过免疫组织化学方法，我们确定了 96 例经根治性切除的胶质瘤患者的 Bax 蛋白表达。进行了两种统计分析来评估 Bax 蛋白的预后意义：独立的连续和多变量分类分析，使用测试/验证集定义的切点，以及 Kaplan-Meier 估计总生存（OS）和无复发生存（RFS）的结果测量。
与 II 级胶质瘤相比，胶质母细胞瘤中的 Bax 蛋白水平显著降低。较低水平的 Bax 表达预示着较差的 OS（连续 P=0.025；分类 P=0.003）和 RFS（连续 P=0.014；分类 P<0.0001），并且与胶质瘤的分级呈负相关。接受放疗继以手术切除的患者显示出显著增加的 OS（中位数=45 个月比 17 个月）和 RFS（中位数=39 个月比 16 个月）。Bax 水平较高且接受放疗的患者的生存率大大提高（中位 OS=66 个月和中位 RFS=105 个月）。Bax 表达较低也预示着接受替莫唑胺化疗的胶质瘤患者的临床结局较差（OS 和 RFS P<0.0001）。
Bax 表达降低与胶质瘤患者的不良临床结局相关。我们提出，Bax 蛋白水平可以作为胶质瘤患者在根治性切除和放疗和/或化疗后进行风险分层的可靠预后标志物。
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