替莫唑胺联合γ-分次立体定向放疗治疗非小细胞肺癌脑转移瘤对S100B、外泌体微小RNA-330表达的影响

The effects of temozolomide combined with γ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330 for non-small cell lung cancer patients with brain metastases

目的探讨替莫唑胺联合γ-分次立体定向放疗治疗非小细胞肺癌(NSCLC)脑转移瘤对S100B、外泌体微小RNA-330(miR-330)表达的影响。方法前瞻性选取2018年2月至2020年10月82例NSCLC脑转移瘤患者为研究对象,按随机数字表法分为对照组和观察组,每组41例。对照组给予γ-分次立体定向放疗,观察组在对照组治疗基础上联合替莫唑胺治疗。比较两组的疗效及预后情况;比较两组治疗前后血清髓鞘碱性蛋白(MBP)、神经元特异性烯醇化酶(NSE)、神经胶质纤维酸性蛋白(GFAP)水平及肝肾功能指标、血清S100B、癌胚抗原(CEA)、外泌体miR-330水平;采用简易智能精神状态检查量表(MMSE)、美国国立卫生院神经功能缺损评分(NIHSS)评价两组患者脑神经功能并进行比较。结果观察组总缓解率高于对照组[65.85%(27/41)比34.15%(14/41)],差异有统计学意义(χ^(2)=8.24,P<0.05)。两组疾病控制率比较差异无统计学意义(P>0.05)。观察组治疗后血清MBP、GFAP及NSE水平均低于对照组[(10.13±2.07)μg/L比(14.39±2.58)μg/L、(0.57±0.12)μg/L比(0.75±0.16)μg/L、(5.09±1.16)μg/L比(7.17±1.35)μg/L],差异有统计学意义(P<0.05)。两组治疗后丙氨酸氨基转移酶、尿素氮、血肌酐水平比较差异无统计学意义(P>0.05)。观察组治疗后NIHSS评分低于对照组[(4.16±0.52)分比(4.73±0.44)分],MMSE评分高于对照组[(22.07±2.51)分比(20.68±2.19)分],差异有统计学意义(P<0.05)。观察组治疗后血清S100B、CEA水平均低于对照组[(62.37±10.54)mg/L比(68.05±9.39)mg/L、(12.61±2.05)μg/L比(14.08±1.97)μg/L],外泌体miR-330表达高于对照组(0.49±0.12比0.42±0.05),差异有统计学意义(P<0.05)。观察组中位生存时间为14.6个月,对照组为11.50个月;两组各项不良反应发生率比较差异均无统计学意义(P>0.05)。结论对NSCLC脑转移瘤患者给予替莫唑胺联合γ-分次立体定向放疗,可提高疗效,改善神经功能,抑制血清S100B、CEA及外泌体miR-330表达,延长生存时间。

Objective To investigate the effects of temozolomide combined withγ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330(miR-330)in the treatment of non-small cell lung cancer(NSCLC)patients with brain metastases.Methods A total of 82 patients with NSCLC brain metastases from February 2018 to October 2020 were selected prospectively,and they were divided into the control group and the observation group by the random number table method,each with 41 patients.The control group receivedγ-fractional stereotactic radiotherapy,and the observation group received temozolomide on the basis of the control group.The therapeutic efficacy and prognosis of the two groups were compared,and the levels of serum myelin basic protein(MBP),neuron-specific enolase(NSE),glial fibrillary acidic protein(GFAP)levels,liver and kidney function indexes,serum S100B,carcinoembryonic antigen(CEA),exosomal miR-330 were compared between the two groups before and after the treatment.The neurologic function of the patients were evaluated by Mini Mental State Examination(MMSE)and National Institutes Health Stroke Scale(NIHSS).Results The total remission rate in the observation group was higher than that in the control group:65.85%(27/41)vs.34.15%(14/41),there was statistical differences(χ^(2)=8.24,P<0.05),but the disease control rate between the two groups had no significant difference(P>0.05).After the treatment,the levels of serum MBP,GFAP and NSE in the observation group were lower than those in the control group:(10.13±2.07)μg/L vs.(14.39±2.58)μg/L,(0.57±0.12)μg/L vs.(0.75±0.16)μg/L,(5.09±1.16)μg/L vs.(7.17±1.35)μg/L,there were statistical differences(P<0.05).The levels alanine aminotransferase,blood urea nitrogen and serum creatinine after treatment between the two groups had no significant differences(P>0.05).After the treatment,the NIHSS scores in the observation group was lower than that in the control group,MMSE scores was higher than that in the control group:(4.16±0.52)scores vs.(4.73±0.44)scores,(22.07±2.51)scores vs.(20.68±2.19)scores,there were statistical differences(P<0.05).After treatment,the serum levels of S100B and CEA in the observation group were lower than those in the control group,and the expression of exosomal miR-330 was higher than that in the control group:(62.37±10.54)mg/L vs.(68.05±9.39)mg/L,(12.61±2.05)μg/L vs.(14.08±1.97)μg/L,0.49±0.12 vs.0.42±0.05,there were statistical differences(P<0.05).The median survival time in the observation group was 14.6 months,while that in the control group was 11.50 months.There were no significant differences in the incidence of adverse reactions between the two groups(P>0.05).Conclusions Treatment with temozolomide combined withγ-fractional stereotactic radiotherapy for NSCLC patients with brain metastases can improve the therapeutic efficacy,neurological function,inhibit the expression of serum S100B,CEA and exosomal miR-330,and prolong the survival time of patients.