儿童髓母细胞瘤组织脑视蛋白3表达与预后的关系

Relationship between Opsin 3 in pediatric medulloblastoma and prognosis

目的 观察髓母细胞瘤患儿癌组织脑视蛋白3(OPN3)表达情况,探讨OPN3表达与预后的关系。方法 2010年1月—2019年12月新疆医科大学第一附属医院行手术治疗髓母细胞瘤患儿61例,取手术切除癌组织,采用免疫组织化学SP法检测OPN3表达。将61例患儿依据OPN3表达情况分为OPN3阳性组38例和OPN3阴性组23例,比较2组髓母细胞瘤分子分型、病变部位、合并脑积水及肿瘤转移率、手术切除程度、Ki-67指数等;多因素logistic回归分析髓母细胞瘤患儿OPN3阳性表达的影响因素。随访1~10年,记录61例患儿肿瘤复发和生存情况,比较OPN3阳性组与OPN3阴性组总生存期和无进展生存期。61例患儿中生存21例为生存组、死亡40例为死亡组,比较生存组与死亡组分子分型、病变部位、合并脑积水及肿瘤转移率、手术切除程度、Ki-67指数、OPN3表达及术后放、化疗情况;多因素Cox回归分析髓母细胞瘤患儿术后死亡的影响因素。结果 (1)OPN3阳性组SHH型比率(65.8%)高于OPN3阴性组(34.8%)(χ^(2)=6.814,P=0.033),病变位于小脑半球比率(7.9%)低于OPN3阴性组(34.8%)(χ^(2)=8.681,P=0.031),性别比例、年龄、Ki-67指数、手术切除程度、合并脑积水及肿瘤转移率与OPN3阴性组比较差异均无统计学意义(P>0.05)。SHH型是髓母细胞瘤OPN3阳性表达的危险因素(OR=18.56,95%CI:2.846~121.020,P=0.002)。(2)随访至2021年12月,中位随访23(11,40)个月,死亡40例中OPN3阳性表达29例,OPN3阴性表达11例;肿瘤复发5例中OPN3阳性表达2例,OPN3阴性表达3例。OPN3阳性组总生存期[17(7,34)个月]、无进展生存期[15(6,32)个月]均短于OPN3阴性组[40(29,73)、40(25,73)个月](χ^(2)=4.407,P<0.001;χ^(2)=4.117,P<0.001)。(3)死亡组OPN3阳性表达(72.5%)、SHH型(62.5%)比率均高于生存组(42.9%、38.1%)(χ^(2)=17.706,P<0.001;χ^(2)=9.953,P=0.009),术后放疗(32.5%)、化疗(20.0%)比率均低于生存组(85.7%、76.2%)(χ^(2)=12.820,P<0.001;χ^(2)=15.694,P<0.001),性别比例、年龄、病变部位、手术切除程度、合并脑积水及肿瘤转移率与生存组比较差异均无统计学意义(P>0.05)。SHH型(HR=2.590,95%CI:1.073~6.252,P<0.001)、OPN3阳性表达(HR=6.918,95%CI:2.787~17.174,P<0.001)是髓母细胞瘤患儿术后死亡的危险因素。结论 SHH型髓母细胞瘤OPN3阳性表达率高,OPN3阳性表达者术后易复发、预后差;SHH型、OPN3阳性表达是髓母细胞瘤患儿预后不良的影响因素。

Objective To observe the expression of Opsin 3(OPN3) in pediatric medulloblastoma,and to explore its relationship with the prognosis.Methods From January 2010 to December 2019,61 children with medulloblastoma underwent surgery in the First Affiliated Hospital of Xinjiang Medical University.The expression of OPN3 in the resected medulloblastoma tissues was detected by immunohistochemical staining SP method,and 61 patients were divided into OPN3 positive group(n=38) and OPN3 negative group(n=23).The molecular type,lesion site,hydrocephalus,metastasis rate,degree of surgical resection,and Ki-67 index of medulloblastoma were compared between two groups.Multivariate logistic regression analysis was done to assess the influencing factors of positive expression of OPN3 in children with medulloblastoma.The follow-up survey was done for 1 to 10 years to record the tumor recurrence and survival of 61 children,and the overall survival and progression-free survival were compared between two groups.Sixty-one patients were divided into survival group(n=21) and death group(n=40),and the molecular type,lesion site,hydrocephalus,metastasis rate,degree of surgical resection,Ki-67 index,OPN3 expression and postoperative radiotherapy and chemotherapy were compared between two groups.Multivariate Cox regression analysis was done to assess the influencing factors of postoperative death in children with medulloblastoma.Results(1) The proportion of SHH type was higher in OPN3 positive group(65.8%) than that in OPN3 negative group(34.8%)(χ^(2)=6.814,P=0.033),the proportion of lesions locating in cerebellar hemisphere was lower in OPN3 positive group(7.9%) than that in OPN3 negative group(34.8%)(χ^(2)=8.681,P=0.031),and there were no significant differences in the gender ratio,age,Ki-67 index,degree of surgical resection,hydrocephalus and metastasis rate between two groups(P>0.05).SHH type was a risk factor of OPN3 positive expression in children with medulloblastoma(OR=18.56,95% CI:2.846-121.020,P=0.002).(2) The follow-up was done till December 2021,with a median follow-up time of23(11,40) months,40 patients died including 29 in OPN3 positive group and 11 in OPN3 negative group,and 5 patients developed recurrence including 2 in OPN3 positive group and 3 in OPN3 negative group.The overall survival and progression-free survival were shorter in OPN3 positive group [17(7,34),15(6,,2) months] than those in OPN3negative group [40(29,73),40(25,73) months](χ^(2)=4.407,P<0.001;χ^(2)=4.117,P<0.001).(3) The positive rate of OPN3 and proportion of SHH type were higher in death group(72.5%,62.5%) than those in survival group(42.9%,38.1%)(χ^(2)=17.706,P<0.001;χ^(2)=9.953,P=0.009),the proportions of postoperative radiotherapy and chemotherapy were lower in death group(32.5 %,20.0%) than those in survival group(85.7%,76.2%)(χ^(2)=12.820,P<0.001;χ^(2)=15.694,P<0.001),and there were no significant differences in the gender ratio,age,lesion site,degree of surgical resection,hydrocephalus and metastasis rate between two groups(P>0.05).SHH type(HR=2.590,95%CI:1.073-6.252,P<O.001) and OPN3 positive expression(HR=6.918,95%CI:2.787-17.174,P<0.001) were the risk factors of postoperative death in children with medulloblastoma.Conclusions The positive rate of OPN3 is high in children with SHH type medulloblastoma.The patients with OPN3 positive expression are prone to recurrence and poor prognosis.The positive expression of OPN3 and SHH type are the influencing factors of poor prognosis of children with medulloblastoma.