Liang Zhuangzhuang,Zhao Heng,Wang Jiajia,et al.Effect of Ki-67 expression on prognosis of pediatric medulloblastoma[J].Journal of Clinical Pediatric Surgery,2022,21(08):746-751.[doi:10.3760/cma.j.cn101785-202105017-008]
Ki-67表达对儿童髓母细胞瘤预后的影响研究
- Title:
- Effect of Ki-67 expression on prognosis of pediatric medulloblastoma
- Keywords:
- Medulloblastoma/DI; Biomarkers; Tumor; Medulloblastoma/SU; Treatment Outcome; Child
- 摘要:
- 目的 分析髓母细胞瘤(medulloblastoma,MB)患儿的临床特征及生存情况,初步探讨Ki-67对MB患儿预后的影响。方法 以2006年1月至2015年12月上海交通大学医学院附属新华医院小儿神经外科收治的67例术后病理证实为MB的患儿为研究对象,采用Kaplan-Meier法计算患儿5年生存时间(overall survival,OS)和无进展生存时间(progression free survival,PFS)。MB患儿预后相关因素的单因素分析采用Log-rank检验,多因素分析采用Cox回归。结果 67例MB患儿Ki-67指数为(34.85 ±16.72)%,Ki-67低表达(<35%)组37例,5年PFS为70.27%(26/37)、OS为51.35%(19/37);Ki-67高表达(≥ 35%)组30例,5年PFS为40.00%(12/30),OS为36.67%(11/30);Cox比例风险回归模型显示:Ki-67高表达是儿童MB生存时间短的独立影响因素(P=0.04),但与术后转移、复发无关(P>0.05)。结论 Ki-67指数可作为评估儿童MB预后的重要独立预测生物标志物。
- Abstract:
- Objective To explore the clinical characteristics and survival profiles of pediatric medulloblastoma and examine the effect of Ki-67 on its prognosis.Methods From January 2006 to December 2015,a total of 67 postoperatively pathologically confirmed MB children were recruited.Their 5-year overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method.Univariate analysis was performed by Log-rank test and multivariate analysis by Cox regression.The relationship was examined between clinical characteristics of MB,treatments and the expression of Ki-67 on the prognosis.Results The average Ki-67 index was (34.85±16.72%).There were 37 cases in low-expression of Ki-67 group (<35%),5-year PFS (70.27%,26/37) and OS (51.35%,19/37);30 cases in high-expression of Ki-67 group (≥ 35%),5-year PFS (40.00%,12/30) and OS (36.67%,11/30).Cox proportional risk regression model showed that a high expression of Ki-67 was an independent factor for MB survival in children (P=0.04).However,no statistically significant difference existed in postoperative metastasis or recurrence.Conclusion Ki-67 is an independent prognostic biomarker for pediatric MB.
参考文献/References:
[1] Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.DOI:10.3322/caac.21332.
[2] Liu X,Ding C,Tan W,et al.Medulloblastoma:molecular understanding,treatment evolution,and new developments[J].Pharmacol Ther,2020,210:107516.DOI:10.1016/j.pharmthera.2020.107516.
[3] 中国抗癌协会小儿肿瘤专业委员会.儿童髓母细胞瘤多学科诊疗专家共识(CCCG-MB-2017)[J].中国小儿血液与肿瘤杂志,2018,23(4):169-174.DOI:10.3969/j.issn.1673-5323.2018.04.001. Committee of Pediatrics,Chinese Anti-Cancer Association,Multidisciplinary therapists Consensus on Pediatric Medulloblastoma[J].Journal of China Pediatric Blood and Cancer,2018,23(4):169-174.DOI:10.3969/j.issn.1673-5323.2018.04.001.
[4] Kool M,Korshunov A,Remke M,et al.Molecular subgroups of medulloblastoma:an international meta-analysis of transcriptome,genetic aberrations,and clinical data of WNT,SHH,Group 3,and Group 4 medulloblastomas[J].Acta Neuropathol,2012,123(4):473-484.DOI:10.1007/s00401-012-0958-8.
[5] Ramaswamy V,Remke M,Bouffet E,et al.Risk stratification of childhood medulloblastoma in the molecular era:the current consensus[J].Acta Neuropathol,2016,131(6):821-831.DOI:10.1007/s00401-016-1569-6.
[6] Shim KW,Joo SY,Kim SH,et al.Prediction of prognosis in children with medulloblastoma by using immunohistochemical analysis and tissue microarray[J].J Neurosurg Pediatr,2008,1(3):196-205.DOI:10.3171/PED/2008/1/3/196.
[7] Sun X,Kaufman PD.Ki-67:more than a proliferation marker[J].Chromosoma,2018,127(2):175-186.DOI:10.1007/s00412-018-0659-8.
[8] Nielsen TO,Leung S,Rimm DL,et al.Assessment of ki67 in breast cancer:updated recommendations from the international ki67 in breast cancer working group[J].J Natl Cancer Inst,2021,113(7):808-819.DOI:10.1093/jnci/djaa201.
[9] Tian Y,Ma Z,Chen Z,et al.Clinicopathological and prognostic value of ki-67 expression in bladder cancer:a systematic review and meta-analysis[J].PLoS One,2016,11(7):e0158891.DOI:10.1371/journal.pone.0158891.
[10] Zhao F,Zhang J,Li P,et al.Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup:a retrospective clinical and molecular analysis[J].J Neurooncol,2018,139(2):333-340.DOI:10.1007/s11060-018-2865-x.
[11] 李克,耿俊杰,张振宇,等.Ki-67表达对髓母细胞瘤患者预后的影响[J].中国实用医刊,2019,46(11):1-3.DOI:10.3760/cma.j.issn.1674-4756.2019.11.001. Li K,Geng JJ,Zhang ZY,et al.Influence of Ki-67 on the prognosis of patients with medulloblastoma[J].Chinese Journal of Practical Medicine,2019,46(11):1-3.DOI:10.3760/cma.j.issn.1674-4756.2019.11.001.
[12] Thompson EM,Hielscher T,Bouffet E,et al.Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup:a retrospective integrated clinical and molecular analysis[J].Lancet Oncol,2016,17(4):484-495.DOI:10.1016/S1470-2045(15)00581-1.
[13] 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(6):803-820.DOI:10.1007/s00401-016-1545-1.
[14] Chang CH,Housepian EM,Herbert C Jr.An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas[J].Radiology,1969,93(6):1351-1359.DOI:10.1148/93.6.1351.
[15] 余建忠,施伟,赵瑞,等.儿童髓母细胞瘤的临床特点及预后相关因素分析[J].临床小儿外科杂志,2020,19(3):236-240,247.DOI:10.3969/j.issn.1671-6353.2020.03.009. Yu JZ,Shi W,Zhao R,et a1.Clinical characteristics and prognostic factors of pediatric medulloblastoma[J].J Clin Ped Sur,2020,19(3):236-240,247.DOI.10.3969/j.issn.1671-6353.2020.03.009.
[16] Nam DH,Wang KC,Kim YM,et al.The effect of isochromosome 17q presence,proliferative and apoptotic indices,expression of c-erbB-2,bcl-2 and p53 proteins on the prognosis of medulloblastoma[J].J Korean Med Sci,2000,15(4):452-456.DOI:10.3346/jkms.2000.15.4.452.
[17] Son EI,Kim IM,Kim DW,et al.Immunohistochemical analysis for histopathological subtypes in pediatric medulloblastomas[J].Pathol Int,2003,53(2):67-73.DOI:10.1046/j.1440-1827.2003.01444.x.
[18] Woodburn RT,Azzarelli B,Montebello JF,et al.Intense p53 staining is a valuable prognostic indicator for poor prognosis in medulloblastoma/central nervous system primitive neuroectodermal tumors[J].J Neurooncol,2001,52(1):57-62.DOI:10.1023/a:1010691330670.
[19] Cuylen S,Blaukopf C,Politi AZ,et al.Ki-67 acts as a biological surfactant to disperse mitotic chromosomes[J].Nature,2016,535(7611):308-312.DOI:10.1038/nature18610.
[20] MacCallum DE,Hall PA.The biochemical characterization of the DNA binding activity of pKi67[J].J Pathol,2000,191(3):286-298.DOI:10.1002/1096-9896(2000)9999:9999<::AID-PATH628>3.0.CO;2-J.
[21] Gerdes J,Lemke H,Baisch H,et al.Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67[J].J Immunol,1984,133(4):1710-1715.
[22] D’cunja J,Shalaby T,Rivera P,et al.Antisense treatment of IGF-IR induces apoptosis and enhances chemosensitivity in central nervous system atypical teratoid/rhabdoid tumours cells[J].Eur J Cancer,2007,43(10):1581-1589.DOI:10.1016/j.ejca.2007.03.003.
[23] 苗娜,楚慧,王志强,等.85例髓母细胞瘤临床病理学分析[J].新疆医科大学学报,2015,38(1):77-79.DOI:10.3969/j.issn.1009-5551.2015.01.020. Miao N,Chu H,Wang ZQ,et al.Clinicopathological ananlysis of 85 cases with medulloblastoma[J].Journal of Xinjiang Medical University,2015,38(1):77-79.DOI:10.3969/j.issn.1009-5551.2015.01.020.
[24] Zhang ZY,Xu J,Ren Y,et al.Medulloblastoma in China:clinicopathologic analyses of SHH,WNT,and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy[J].PLoS One,2014,9(6):1932-6203.DOI:10.1371/journal.pone.0099490.
备注/Memo
收稿日期:2021-5-12。
基金项目:上海市科委(19411952100)
通讯作者:马杰,Email:majie@xinhuamed.com.cn