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Value of MORC2-IDH1 detection in molecular subtyping of glioblastoma patients treated with postoperative chemoradiotherapy
Tang Meng, Xu Hui, Wang You, Ding Qianshan, Zhou Fuxiang
Department of Radiation & Medical Oncology,Zhongnan Hospital of Wuhan University,Clinical CancerStudy Center,Key Laboratory of Tumor Biological Behavior of Hubei Province,Wuhan 430071,China
AbstractObjective 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 IDH1mt/MORC2lowobtained the best clinical prognosis with a median survival of 22 months (95%CI:13.98-30.02), whereas those with the subtype of IDH1wt/MORC2highobtained 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 IDH1wtglioblastoma patients, MORC2highpatients had worse clinical prognosis compared with MORC2lowcounterparts, prompting that IDH1wt/MORC2highglioblastoma 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.
Tang Meng,Xu Hui,Wang You et al. Value of MORC2-IDH1 detection in molecular subtyping of glioblastoma patients treated with postoperative chemoradiotherapy[J]. Chinese Journal of Radiation Oncology, 2019, 28(6): 401-404.
Tang Meng,Xu Hui,Wang You et al. Value of MORC2-IDH1 detection in molecular subtyping of glioblastoma patients treated with postoperative chemoradiotherapy[J]. Chinese Journal of Radiation Oncology, 2019, 28(6): 401-404.
[1] Louis DN,Perry A,Reifenberger G,et al. The 2016 World Health Organization classification of tumors of the central nervous system:a summary[J].Acta Neuropathol,2016,131(4):803-820.DOI:10.1007/s00401-016-1545-1. [2] Colman H,Zhang L,Sulman EP,et al. A multigene predictor of outcome in glioblastoma[J].Neuro Oncol,2010,12(1):49-57.DOI:10.1093/neuonc/nop007. [3] Ohka F,Yamamichi A,Kurimoto M,et al. A novel all-in-one intraoperative genotyping system for IDH1-mutant glioma[J].Brain Tumor Pathol,2017,34(1):91-97.DOI:10.1007/s10014-017-0281-0. [4] Zhang L,Liu Y,Wang M,et al. EZH2-,CHD4-,and IDH-linked epigenetic perturbation and its association with survival in glioma patients[J].J Mol Cell Biol,2017,9(2):477-488.DOI:10.1093/jmcb/mjx056. [5] Li DQ,Nair SS,Kumar R.The MORC family[J].Epigenetics,2014,8(3):685-693.DOI:10.4161/epi.24976. [6] Ding QS,Zhang L,Wang BC,et al. Aberrant high expression level of MORC2 is a common character in multiple cancers[J].Hum Pathol,2018,76(1):58-67.DOI:10.1016/j.humpath.2018.03.011. [7] Li DQ,Nair SS,Ohshiro K,et al. MORC2 signaling integrates phosphorylation-dependent,ATPase-coupled chromatin remodeling during the DNA damage response[J].Cell Rep,2012,2:1657-1669.DOI:10.1016/j.celrep.2012.11.018. [8] Sánchez-Solana B,Li DQ,Kumar R.Cytosolic functions of MORC2 in lipogenesis and adipogenesis[J].Mol Cell Res,2014,1843(2):316-326.DOI:10.1016/j.bbamcr.2013.11.012. [9] Bollag G,Hirth P,Tsai J,et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma[J].Nature,2010,467(3):596-599.DOI:10.1038/nature09454. [10] Sulman EP,Ismaila N,Chang SM.Radiation therapy for glioblastoma:American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Guideline[J].J Oncol Pract, 2017,13(1):123-127.DOI:10.1200/jop.2016.018937. [11] Wang GL,Wang CY,Cai XZ,et al. Identification and expression analysis of a novel CW-Type zinc finger protein MORC2 in cancer cells. The anatomical record:advances in integrative anatomy[J].Evolut Biol,2010,293(5):1002-1009.DOI:10.1002/ar.21119. [12] Pan Z,Ding Q,Guo Q,et al. MORC2,a novel oncogene,is upregulated in liver cancer and contributes to proliferation,metastasis and chemoresistance[J].Int J Oncol,2018,53(1):59-72.DOI:10.3892/ijo.2018.4333. [13] Victor M,Lu KLM.Isocitrate dehydrogenase 1 mutation subtypes at site 132 and their translational potential in glioma[J].CNS Oncol,2018,7(1):41-50.