联合MORC2-IDH1检测对胶质母细胞瘤放化疗患者分子分型价值

目的 研究MORC2在胶质母细胞瘤组织中的表达及其联合IDH1突变状态对放化疗疗效的预测作用及分子分型价值。方法 应用免疫组化检测45例胶质母细胞瘤组织中MORC2表达水平,分析其与患者临床特征及放化疗预后间关系。通过胶质瘤转录组数据库进一步联合分析MORC2转录水平及IDH1突变状态对胶质母细胞瘤患者放化疗预后意义。结果 胶质母细胞瘤患者中MORC2蛋白高表达率为76%,且与放化疗预后总生存及无复发生存呈负相关(HR=2.928,95%CI为1.582~5.418,P=0.002;HR=2.204,95%CI为1.186~4.095,P=0.022)。联合IDH1突变状态、MORC2转录水平可将胶质母细胞瘤术后接受放化疗患者分为3个亚型,其中IDH1突变型(IDH1^mt)伴MORC2低表达(MORC2^low)者预后最好,中位生存期为22个月(95%CI为13.98~30.02),而IDH1野生型(IDH1^wt)伴MORC2高表达(MORC2^high)者预后最差,中位生存期为5.63个月(95%CI为3.92~7.34)(HR=4.15,95%CI为1.606~10.720,P=0.002)。在IDH1^wt中MORC2^high比MORC2^low预后更差,提示IDH1^wt/MORC2^high胶质母细胞瘤组织具有更强的DNA损伤修复能力,对放化疗治疗更抗拒。结论 MORC2^high可作为胶质母细胞瘤患者潜在的放化疗预后不良的指标,联合IDH1突变状态及MORC2表达水平可建立一种新的分子分型,为分层治疗提供依据。

Value of MORC2-IDH1 detection in molecular subtyping of glioblastoma patients treated with postoperative chemoradiotherapy

Objective To investigate the expression of microrchidia 2(MORC2) in glioblastoma patients and to evaluate its prognostic value of MORC2 expression combined with IDH1 mutation status for chemoradiotherapy efficacy and new molecular subtype.Methods The expression level of MORC2 in 45 glioblastoma tissues was measured by immunohistochemical staining and its correlation with clinicopathological characteristics and clinical prognosis after chemoradiotherapy was analyzed. Further more,the prognostic values of the expression of MORC2 combined with the status of IDH1 were assessed in a glioblastoma CGGA mRNA dataset.Results High expression of MORC2 was observed in 76% of glioblastoma patients, which was negatively correlated with overall survival (HR=2.928,95%CI:1.582-5.418,P=0.002;recurrence-free survival (HR=2.204,95%CI:1.186-4.095,P=0.022).Moreover,according to the prognosis value of MORC2 expression and IDH1 mutation status, glioblastoma patients were divided into 3 molecular subtypes. Patients with the subtype of IDH1^mt/MORC2^lowobtained the best clinical prognosis with a median survival of 22 months (95%CI:13.98-30.02), whereas those with the subtype of IDH1^wt/MORC2^highobtained the worst clinical prognosis with a median survival of 5.63 months (95%CI:3.92-7.34,HR=4.15,95%CI:3.92-7.34,P=0.002).Among IDH1^wtglioblastoma patients, MORC2^highpatients had worse clinical prognosis compared with MORC2^lowcounterparts, prompting that IDH1^wt/MORC2^highglioblastoma tissues yielded higher capability of DNA injury repairing and resistance to chemoradiotherapy.Conclusions The high expression of MORC2 can be used as a potential indicator of poor prognosis of glioblastoma patients after chemoradiotherapy. IDH1 mutation status combined with MORC2 expression can establish a novel molecular subtyping, which provide evidence for stratified therapy for glioblastoma patients.