IN1基因表达与儿童肝母细胞瘤临床特点及预后的相关性研究

Correlation between IN1 gene expression levels and clinical characteristics and prognosis of hepatoblastoma in childhood

目的研究IN1基因表达水平与儿童肝母细胞瘤(HB)临床特点及疗效的相关性,阐明IN1基因对治疗及预后的预警价值。方法筛选2015年1月至2018年5月首都医科大学附属北京同仁医院确诊的初诊初治HB 40例。采用荧光免疫PCR法检测IN1基因mRNA表达水平。收集HB患儿的临床资料,包括分期、分组、危险度、化疗疗效及预后。应用SPSS 21.0软件分析IN1基因mRNA表达水平与临床疗效、分期、预后的相关性。结果1.临床特点:40例患儿中位年龄(30.50±2.39)个月;男29例(72.5%),女11例(27.5%)。临床分期及分组:Ⅱ期1例(2.5%),Ⅲ期13(32.5%),Ⅳ期26例(65.0%);中低危组12例(30.0%),高危组28例(70.0%)。2.临床疗效及预后:随访至2017年7月1日,随访时间(12.2±10.1)个月,未行根治手术患儿4例(10%),手术治疗36例(90%);所有患儿均行化疗(100%),平均化疗(13.17±0.02)个周期。30例患儿存活,10例患儿死亡,总生存率(OS)75%;无事件生存20例(50%)。3.IN1基因mRNA表达:40例HB患儿IN1基因mRNA平均相对表达定量(2^-ΔCT):0.31±0.70。高危及中高危HB患儿的平均表达定量(2^-ΔCT):0.23±0.43、0.48±1.13(t=6.363,P=0.05);病理未分化小细胞型(12例)与其他病理分型(25例)的平均相对表达定量分别为:0.09±0.11、0.43±0.86(t=4.533,P=0.04)。未根治手术(n=4)及行根治性手术(n=36)患儿平均相对表达定量(2^-ΔCT)分别为0.04±0.03及0.34±0.74,二者比较差异有统计学意义(t=2.935,P=0.022);化疗敏感性差(19例)及化疗敏感患儿(21例)相对表达量(2^-ΔCT)分别为0.03±0.04及0.30±0.82,二者比较差异有统计学意义(t=5.688,P=0.018)。结论IN1基因mRNA呈低表达患儿化疗疗效欠佳。IN1基因低表达在提示临床疗效及预后方面具有积极的预警作用。

Objective To study on the mRNA expression level of IN1 gene associated with the clinical efficacy and prognosis of hepatoblastoma(HB) in children and to elucidate the early warning value of IN1 gene for prognosis and chemotherapy sensitivity. Methods Forty HB patients were selected based on primary diagnosis and treated from January 2015 to May 2018 in Tongren Hospital Affiliated to Capital Medical University. The expression level of INI1 gene was detected by using fluorescence immuno-PCR. Clinical data of children with HB were collected, including staging, grouping, risk, efficacy and prognosis of chemotherapy. The relationship between the mRNA expression of IN1 gene and clinical data was analyzed by SPSS 21.0 software. Results (1)Clinical characters: the medium age of 40 HB patients was(30.50±2.39) months, male 29 cases (72.5%), and female 11 cases (27.5%). There was 1 case (2.5%) of stage Ⅱ HB, 13 cases (32.5%) of stage Ⅲ HB, and 26 cases (65.0%) of stage Ⅳ. The low-and intermediate- risk group had 12 cases (30.0%) of HB, and the high-risk group had 28 cases (70.0%) of HB.(2)Clinical efficacy and prognosis: by July 1st, 2018, the medium following-up time was (12.2±10.1) months, 4 patients (10%) were treated by chemotherapy without surgery, and 36 patients (90%) were treated by surgery .All patients (100%) received chemotherapy.The average cycle of chemotherapy lasted(13.17±0.02). Ten patients were dead and 30 patients survived till following-up.The overall survival (OS) rates were 75% and the event-free survival rates were 50%(20 patients with HB).(3) IN1 gene mRNA expression: The average PCR quantitative of IN1 gene mRNA of 40 HB patients(2^-ΔCT)was 0.31±0.70.The average mRNA quantitative of HB patients (2^-ΔCT)with high-risk and low/intermediate-risk group was 0.23±0.43 and 0.48±1.13(t=6.363, P=0.05). According to histology diagnosis, the average mRNA quantitative of small cell undifferentiated (SCU) type (12 cases)and other type (25 cases) was 0.09±0.11 and 0.43±0.86(t=4.533, P=0.04). The average mRNA quantitative of patients with or without radical surgery was 0.04±0.03 and 0.34±0.74 (t=2.935, P=0.022). The data of children with poor chemotherapy sensitivity(19 cases)and those sensitive to chemotherapy (21 cases) were 0.03±0.04 and 0.30±0.82, and the difference was statistically significant (t=5.688, P=0.018). Conclusions Poor therapeutic effect results in low mRNA expression of IN1 gene in children of HB.The IN1 gene expression could be an early warning factor for treatment sensitivity and prognosis.