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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：我们进行了一项荟萃分析，以全面评估MYC的预测作用，BCL2、BCL6基因改变和蛋白表达在PCNSL中的临床应用。
方法：在PubMed上进行了系统检索，Embase,科克伦图书馆,WebofScience,Scopus,2个中文数据库。队列研究讨论MYC的预后影响，选择PCNSL中的BCl2或BCL6遗传改变或基因表达。计算合并风险比（HR）和中位生存率（MSR）。
结果：涉及1739例患者的31项研究符合我们的纳入标准。MYC表达与短的中位OS(MSR=0.62;95CI,0.44-0.88)和PFS(HR=1.53;95CI,1.06-2.20)显著相关。BCL2表达与OS和PFS无显著相关性(P>0.05)。BCL6蛋白阳性与中位OS延长显著相关(MSR=1.62;95CI,1.10-2.40)。MYC和BCL2共表达与短的中位OS显著相关(MSR=0.61;95CI,0.45-0.84)。亚组分析表明，在样本量≥45，不使用WBRT治疗的研究中，MYC蛋白阳性仍然是短中位OS的重要指标。质量量表评分≥7分，阳性阈值设置在40%层（MSR<1和P<0.05），但在其他地层中未能达到统计学上的显着差异。
结论：MYC表达预测PCNSL的中位OS和PFS较差。BCL6蛋白阳性与良好的预后相关。样本量,受试者的平均年龄,WBRT处理,学习质量,在IHC中区分阳性和阴性蛋白表达的临界值可能是异质性的起源。
方法：在PubMed上进行了系统检索，Embase,科克伦图书馆,WebofScience,Scopus,2个中文数据库。队列研究讨论MYC的预后影响，选择PCNSL中的BCl2或BCL6遗传改变或基因表达。计算合并风险比（HR）和中位生存率（MSR）。
结果：涉及1739例患者的31项研究符合我们的纳入标准。MYC表达与短的中位OS(MSR=0.62;95CI,0.44-0.88)和PFS(HR=1.53;95CI,1.06-2.20)显著相关。BCL2表达与OS和PFS无显著相关性(P>0.05)。BCL6蛋白阳性与中位OS延长显著相关(MSR=1.62;95CI,1.10-2.40)。MYC和BCL2共表达与短的中位OS显著相关(MSR=0.61;95CI,0.45-0.84)。亚组分析表明，在样本量≥45，不使用WBRT治疗的研究中，MYC蛋白阳性仍然是短中位OS的重要指标。质量量表评分≥7分，阳性阈值设置在40%层（MSR<1和P<0.05），但在其他地层中未能达到统计学上的显着差异。
结论：MYC表达预测PCNSL的中位OS和PFS较差。BCL6蛋白阳性与良好的预后相关。样本量,受试者的平均年龄,WBRT处理,学习质量,在IHC中区分阳性和阴性蛋白表达的临界值可能是异质性的起源。
