Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin 300350, China.
Clin Neurol Neurosurg. 2021 Sep;208:106838. doi: 10.1016/j.clineuro.2021.106838. Epub 2021 Jul 22.
We conducted a meta-analysis to comprehensively assess the predictive role of MYC, BCL2, and BCL6 genetic alterations and protein expression in PCNSL for clinical application.
A systematic retrieval was performed on PubMed, Embase, the Cochrane library, Web of Science, Scopus, and 2 Chinese databases. Cohort studies discussing the prognostic impact of MYC, BCl2, or BCL6 genetic alterations or gene expression in PCNSL were selected. The pooled hazard ratio (HR) and median survival ratio (MSR) were calculated.
31 studies involving 1739 patients fulfilled our inclusion criteria. MYC expression was significantly associated with short median OS (MSR = 0.62; 95%CI, 0.44-0.88) and PFS (HR = 1.53; 95%CI, 1.06-2.20). No significant association was found between BCL2 expression and OS or PFS (P > 0.05). BCL6 protein positivity was significantly associated with extended median OS (MSR = 1.62; 95%CI, 1.10-2.40). MYC and BCL2 coexpression was significantly associated with short median OS (MSR = 0.61; 95%CI, 0.45-0.84). Subgroup analysis demonstrated that MYC protein positivity remained as a significant indicator for short median OS in studies whose sample size ≥ 45, treatment without WBRT, quality scale score ≥ 7, and positivity threshold set at 40% stratum (MSR < 1 and P < 0.05), but failed to reach a statistically significant difference in the other stratum.
MYC expression predicts inferior median OS and PFS in PCNSL. BCL6 protein positivity is associated with a favorable prognosis. The sample size, average age of subjects, WBRT treatment, study quality, and cut-off values for discriminating positive and negative protein expression in IHC may be origins of heterogeneity.
我们进行了一项荟萃分析，全面评估了 MYC、BCL2 和 BCL6 基因改变和蛋白表达在原发性中枢神经系统淋巴瘤（PCNSL）中的预测作用，以便于临床应用。
系统检索 PubMed、Embase、Cochrane 图书馆、Web of Science、Scopus 和 2 个中文数据库，纳入探讨 MYC、BCL2 或 BCL6 基因改变或基因表达对 PCNSL 预后影响的队列研究。计算合并的风险比（HR）和中位生存比（MSR）。
纳入 31 项研究，共 1739 例患者。MYC 表达与较短的中位 OS（MSR=0.62；95%CI，0.44-0.88）和 PFS（HR=1.53；95%CI，1.06-2.20）显著相关。BCL2 表达与 OS 或 PFS 无显著相关性（P>0.05）。BCL6 蛋白阳性与较长的中位 OS 显著相关（MSR=1.62；95%CI，1.10-2.40）。MYC 和 BCL2 共表达与较短的中位 OS 显著相关（MSR=0.61；95%CI，0.45-0.84）。亚组分析显示，在样本量≥45 例、未行 WBRT 治疗、质量评分≥7 分、阳性阈值设定为 40%分层（MSR<1，P<0.05）的研究中，MYC 蛋白阳性仍然是中位 OS 较短的显著指标，但在其他分层中未达到统计学差异。
MYC 表达可预测 PCNSL 患者的中位 OS 和 PFS 较短。BCL6 蛋白阳性与预后良好相关。样本量、受试者平均年龄、WBRT 治疗、研究质量和 IHC 中区分阳性和阴性蛋白表达的截断值可能是异质性的来源。
