中西医联合治疗对晚期NSCLC miRNA表达谱的影响
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摘要
目的对中西医联合治疗晚期非小细胞肺癌(NSCLC)获益血清miRNA表达谱进行初步研究,探讨晚期NSCLC疗效监测和预测分子标记物。方法选取5例接受中西医联合治疗且疗效获益的晚期NSCLC患者(简称治疗组)和3例晚期NSCLC初治患者(简称肺癌组)及3名健康体检者(简称对照组),采集血清标本并用Trizol法提取总RNA,运用Exiqon公司microRNA PCR ARRAY芯片技术筛选检测肺癌组血清与对照组血清中差异miRNA表达谱、治疗组血清与肺癌组血清差异miRNA表达谱,基于聚类分析及对比分析,进一步得到中西医联合治疗晚期NSCLC获益miRNA表达谱。结果经microRNA PCR ARRAY检测和数据分析处理后,肺癌组与对照组共筛选出42个差异在2倍以上的miRNAs,其中29个为上调的miRNAs,13个为下调的miRNAs;且miR-10b-5p、miR-21-5p、miR-182-5p、miR-361-3p、miR-382-5p差异有统计学意义(P<0.05)。治疗组与肺癌组筛选出45个差异在2倍以上的miRNAs,其中12个上调的miRNAs,33个下调的miRNAs;miR-137-3p、miR-182-5p、miR-376a-3p、miR-382-5p、miR-409-3p、miR-10a-5p、miR-21-5p、miR-29a-3p、miR-141-3p、miR-150-5p、miR-200c-3p、miR-342-3p、miR-365a-3p、miR-375、miR-502-3p 15个miRNAs差异有统计学意义(P<0.05)。治疗组与肺癌组差异倍数>2倍,与对照组差异倍数≤2倍的血清miRNA共筛选出22个,其中7个为上调miRNAs,15个为下调miRNAs;miR-127-3p、miR-182-5p、miR-382-5p、miR-409-3p、miR-10a-5p、miR-21-5p、miR-141-3p、miR-342-3p 8个miRNAs差异有统计学意义(P<0.05)。结论包括miR-21-5p、miR-182-5p、miR-382-5p在内的差异miRNAs有望成为中西医联合治疗晚期NSCLC疗效监测和预测分子标记物;为中西医联合治疗晚期NSCLC个体化治疗提供参考。
Objective To preliminarily observe miRNA gene profiles in benefit serum of advanced non-small cell lung cancer(NSCLC) treated by TCM combined Western medicine(WM),and to seek for molecular markers for its efficacy monitoring and prediction.Methods Recruited were 5 advanced NSCLC patients who received TCM combined WM treatment and obtained efficacy benefit(as the treatment group),3 advanced NSCLC patients who received early treatment(as the lung cancer group),and 3 healthy subjects(as the control group).Serum samples were collected and total RNA was extracted using Trizol method.Using microRNA PCR ARRAY chip technology(product of Exiqon Company),differentially miRNA expression profiling in serum between the lung cancer group and the control group,and between the treatment group and the lung cancer group were detected.Benefit miRNA expression profiling was obtained based on cluster analysis and comparative analysis.Results After tested by miRNA PCR ARRAY and managed by data analysis,a total of 42 miRNAs with more than 2 folds difference were screened in the lung cancer group and the control group,including 29 up-regulated and12 down-regulated miRNAs.Besides,miR-10b-5p,miR-21-5p,miR-182-5p,miR-361-3p,and miR-382-6p were statistically different(P<0.05).A total of 45 miRNAs with more than 2 folds difference were screened in the treatment group and the lung cancer group,including 12up-regulated and 33down-regulated miRNAs.Fifteen miRNAs were statistically different including miR-137-3p,miR-182-5p,miR-376a-3p,miR-382-5p,miR-409-3p,miR-10a-5p,miR-21-5p,miR-29a-3p,miR-141-3p,miR-150-5p,miR-200c-3p,miR-342-3p,miR-365a-3p,miR-375,miR-502-3p(P<0.05).Totally 22 miRNAs were screened in the treatment group with more than 2 folds difference as compared with the lung cancer group and with less than or equivalent to 2 folds difference as compared with the control group,including 7 up-regulated and 15down-regulated miRNAs,of which,miR-127-3p,miR-182-5p,miR-382-5p,miR-409-3p,miR-10a-5p,miR-21-5p,miR-141-3p,miR-342-3p were statistically different(P<0.05).ConclusionmiRNAs including miR-21-5p,miR-182-5p,miR-382-5p are promising to become molecular markers for efficacy monitoring and prediction of advanced NSCLC treated by TCM combined WM,which provides reference for individualized treating advanced NSCLC.
Objective To preliminarily observe miRNA gene profiles in benefit serum of advanced non-small cell lung cancer(NSCLC) treated by TCM combined Western medicine(WM),and to seek for molecular markers for its efficacy monitoring and prediction.Methods Recruited were 5 advanced NSCLC patients who received TCM combined WM treatment and obtained efficacy benefit(as the treatment group),3 advanced NSCLC patients who received early treatment(as the lung cancer group),and 3 healthy subjects(as the control group).Serum samples were collected and total RNA was extracted using Trizol method.Using microRNA PCR ARRAY chip technology(product of Exiqon Company),differentially miRNA expression profiling in serum between the lung cancer group and the control group,and between the treatment group and the lung cancer group were detected.Benefit miRNA expression profiling was obtained based on cluster analysis and comparative analysis.Results After tested by miRNA PCR ARRAY and managed by data analysis,a total of 42 miRNAs with more than 2 folds difference were screened in the lung cancer group and the control group,including 29 up-regulated and12 down-regulated miRNAs.Besides,miR-10b-5p,miR-21-5p,miR-182-5p,miR-361-3p,and miR-382-6p were statistically different(P<0.05).A total of 45 miRNAs with more than 2 folds difference were screened in the treatment group and the lung cancer group,including 12up-regulated and 33down-regulated miRNAs.Fifteen miRNAs were statistically different including miR-137-3p,miR-182-5p,miR-376a-3p,miR-382-5p,miR-409-3p,miR-10a-5p,miR-21-5p,miR-29a-3p,miR-141-3p,miR-150-5p,miR-200c-3p,miR-342-3p,miR-365a-3p,miR-375,miR-502-3p(P<0.05).Totally 22 miRNAs were screened in the treatment group with more than 2 folds difference as compared with the lung cancer group and with less than or equivalent to 2 folds difference as compared with the control group,including 7 up-regulated and 15down-regulated miRNAs,of which,miR-127-3p,miR-182-5p,miR-382-5p,miR-409-3p,miR-10a-5p,miR-21-5p,miR-141-3p,miR-342-3p were statistically different(P<0.05).ConclusionmiRNAs including miR-21-5p,miR-182-5p,miR-382-5p are promising to become molecular markers for efficacy monitoring and prediction of advanced NSCLC treated by TCM combined WM,which provides reference for individualized treating advanced NSCLC.
引文
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[2]Krauskopf J,Verheijen M,Kleinjans JC,et al.Development and regulatory application of microRNA biomarkers[J].Biomark Med,2015,9(11):1137-1151.
[3]支修益,吴一龙,马胜林,等.原发性肺癌诊疗规范(2011年版)[J].中国肺癌杂志,2012,15(12):677-688.
[4]周岱翰主编.中医肿瘤学[M].北京:中国中医药出版社,2011:200-201.
[5]Shen J,Todd NW,Zhang H,et al.Plasma microRNAs as potential biomarkers for non-small-cell lung cancer[J].Lab Invest,2011,91(4):579-587.
[6]Acunzo M,Visone R,Romano G,et al.miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221&222[J].Oncogene,2012,31(5):634-642.
[7]林丽珠,周岱翰,郑心婷.中医药提高晚期NSCLC患者生存质量的临床观察[J].中国中西医结合杂志,2006,26(5):389-393.
[8]王淑美,林丽珠,张文亮,等.中医标本理论在癌症姑息治疗中的应用及价值[J].中医杂志,2011,52(12):997-999.
[9]张辉,张成,苏式兵,等.miRNA与中医药抗癌机制研究的思考[J].中国中医基础医学杂志,2009,15(12):960-962.
[10]Davis BN,Hata A.microRNA in cancer—the involvement of aberrant microRNA biogenesis regulatory pathways[J].Genes Cancer,2010,1(11):1100-1114.
[11]Wei J,Gao W,Zhu CJ,et al.Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer[J].Chin J Cancer,2011,30(6):407-414.
[12]Wang ZX,Bian HB,Wang JR,et al.Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer[J].J Surg Oncol,2011,104(7):847-851.
[13]Liu XG,Zhu WY,Huang YY,et al.High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer[J].Med Oncol,2012,29(2):618-626.
[14]Zhang L,Liu T,Huang Y,et al.microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein[J].Int J Mol Med,2011,28(3):381-388.
[15]Hirata H,Ueno K,Shahryari V,et al.Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer[J].PLo S One,2012,7(11):1-8.
[16]Wang YQ,Guo RD,Guo RM,et al.microRNA-182 promotes cell growth,invasion,and chemoresistance by targeting programmed cell death 4 in human ovarian carcinomas[J].J Cell Biochem,2013,114(7):1464-1473.