低级别胶质瘤术后复发和恶性转化的分子标志物及其预测价值

Molecular markers of postoperative recurrence and malignant transformation in low-grade gliomas and their predictive value

目的探索低级别胶质瘤(low-grade glioma,LGG)患者术后出现复发及恶性转化(malignant transformation,MT)的危险因素。方法回顾性收集2009年3月至2019年4月接受LGG切除手术及随后进行术后随访的163例患者资料。将术后未出现复发或MT的患者纳入对照组(85例),术后出现复发的患者纳入观察1组(44例),术后出现MT的患者纳入观察2组(34例)。基于3组患者的临床资料,分析患者临床特征,并运用Logistic回归模型和受试者工作特征(receiver operating characteristic,ROC)曲线探讨复发和MT的危险因素与预测价值。结果对照组和观察1组患者在术前癫痫发作、术前卡氏(Karnofsky performance status,KPS)评分和手术方式方面均有统计学差异(P<0.05)。对照组和观察2组患者在性别、术前KPS评分、肿瘤大小和手术方式方面均有统计学差异(P<0.05)。对照组和观察1组患者在异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、癌—睾丸抗原OY-TES-1、OY-TES-1 mRNA、肿瘤抑制蛋白p53、鼠双微粒体2(mouse double minute 2,MDM2)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、表皮生长因子受体(epidermal growth factor receptor,EGFR)均有统计学差异(P<0.05)。对照组和观察2组患者PCNA、MMP-9、癌—睾丸抗原OY-TES-1、OY-TES-1 mRNA和VEGF均有统计学差异(P<0.05)。Logistic回归分析结果显示IDH突变、MMP-9和PCNA是LGG复发的独立危险因素(P<0.05),VEGF、MMP-9和PCNA是LGG患者MT的独立危险因素(P<0.05)。PCNA、MMP-9和IDH突变对预测LGG术后复发的曲线下面积(area under curve,AUC)分别为0.744、0.790和0.799。PCNA、MMP-9和VEGF对预测LGG术后复发的AUC分别为0.729、0.750和0.900。结论IDH突变、MMP-9和PCNA是LGG复发的独立危险因素,VEGF、MMP-9和PCNA是LGG MT的独立危险因素。这些蛋白在预测LGG术后复发和MT方面具有较高的准确性,可能在LGG的生物学行为和治疗效果中起重要作用,可以作为LGG术后患者的预后评估和个体化治疗的参考指标。

Objective To identify the risk factors for recurrence and malignant transformation(MT) in patients with low-grade glioma(LGG) after surgery.Methods The data of 163 patients who underwent LGG resection and subsequent follow-up from March 2009 to April 2019 were retrospectively collected.Patients who did not experience recurrence or MT after surgery were included in the control group(85 cases),those who experienced recurrence after surgery were included in the observation 1 group(44 cases),and those who experienced MT after surgery were included in the observation 2 group(34 cases).Based on the clinical data of the three groups of patients,their clinical characteristics were analyzed,and the risk factors and predictive value for recurrence and MT were explored using Logistic regression model and receiver operating characteristic(ROC) curve.Results There were significant differences between the control group and the observation 1 group in preoperative seizure,preoperative Karnofsky performance status(KPS) score,and surgical approach(P<0.05).There were significant differences between the control group and the observation 2 group in gender,preoperative KPS score,tumor size,and surgical approach(P<0.05).There were significant differences between the control group and the observation 1 group in isocitrate dehydrogenase(IDH) mutation,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-9(MMP-9),cancer-testis antigen OY-TES-1,OY-TES-1 mRNA protein,tumor suppressor protein p53,mouse double minute 2(MDM2),vascular endothelial growth factor(VEGF),or epidermal growth factor receptor(EGFR)(P<0.05).There were significant differences between the control group and the observation 2 group in PCNA,MMP-9,cancer-testis antigen OY-TES-1,OY-TES-1 mRNA protein,or VEGF(P<0.05).Logistic regression analysis showed that IDH mutation,MMP-9,and PCNA were independent risk factors for LGG recurrence(P<0.05),while VEGF,MMP-9,and PCNA were independent risk factors for LGG MT(P<0.05).The area under curve(AUC) of PCNA,MMP-9 and IDH mutation for predicting LGG MT after surgery was 0.744,0.790,and 0.799,respectively.The AUC of PCNA,MMP-9,and VEGF for predicting LGG recurrence after surgery was 0.729,0.750,and 0.900,respectively.Conclusion This study found that IDH mutation,MMP-9 and PCNA were independent risk factors for LGG recurrence,while VEGF,MMP-9 and PCNA were independent risk factors for LGG MT by retrospectively analyzing the clinical data and protein expression of 163 patients with LGG after surgery.These proteins have high accuracy in predicting LGG recurrence and MT after surgery.Therefore,the proteins may play an important role in the biological behavior and treatment effect of LGG,and can be used as reference indicators for prognosis evaluation and individualized treatment of LGG patients after surgery.