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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 study the serum miRNA expression profiles of patients with advanced non-small cell lung cancer (NSCLC) treated by Integrative Chinese and Western Medicine (TCM) and to explore the efficacy and prognostic markers of advanced NSCLC. Methods Five NSCLC patients (referred to as treatment group) and 3 newly diagnosed NSCLC patients (referred to as lung cancer group) and 3 healthy subjects (control group) were enrolled in this study. The serum samples The total RNA was extracted by Trizol method. The differentially expressed miRNAs in the serum of the lung cancer group and the control group were detected by Exiqon microRNA PCR ARRAY chip technique. The differential miRNA expression profiles in the serum of the treated group and the lung cancer group were analyzed by cluster analysis and comparative analysis. Further TCM and WM combined treatment of advanced NSCLC to obtain miRNA expression profile. Results After microRNA PCR ARRAY detection and data analysis, 42 miRNAs with more than 2-fold difference were screened from lung cancer group and control group, of which 29 were upregulated miRNAs and 13 were downregulated miRNAs; and miR-10b- 5p, miR-21-5p, miR-182-5p, miR-361-3p and miR-382-5p were significantly different (P <0.05). Forty-five miRNAs with more than 2-fold difference were screened from the treatment group and the lung cancer group, including 12 miRNAs up-regulated and 33 down-regulated miRNAs; miR-137-3p, miR-182-5p, miR-376a-3p, miR- 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 and miR-502-3p 15 miRNAs were significantly different (P <0.05). Twenty-two serum miRNAs were screened in the treatment group and the lung cancer group with a multiple of 2 times greater than that of the control group, with 7 of them being upregulated miRNAs and 15 being downregulated miRNAs; miR-127-3p, miR-182 There were significant differences in 8 miRNAs between 5p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-141-3p and miR- ). Conclusions Differentiated miRNAs including miR-21-5p, miR-182-5p and miR-382-5p are expected to be the molecular markers for the treatment of advanced NSCLC combined with traditional Chinese and western medicine. For the treatment of advanced NSCLC with integrated traditional Chinese and western medicine for reference.