循环miR-29a和miR-150与非小细胞肺癌胸部放射治疗剂量的相关性
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摘要
目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)胸部放射治疗剂量与循环血miR-29a和miR-150的相关性。方法:收集56例2014年1月至2015年12月在我院接受放射治疗的诊断为NSCLC的患者,其中5例NSCLC患者在0、20、40、60 Gy辐照后用miRNA芯片检测循环血miRNA表达差异;51例NSCLC患者在0、20、40 Gy辐照后用实时定量PCR验证循环血中候选miRNA表达;医用直线加速器(2 Gy/天,连续处理3天)辐照A549和MRC5细胞,实时定量PCR检测细胞内和细胞上清外泌体miR-29a和miR-150的表达。结果:miRNA芯片筛选出随着患者放疗剂量的增加而差异表达的10个miRNA(miR-29a、miR-150、miR-142、miR-342、miR-125b、miR-101、miR-425、miR-338、miR-126、miR-15b)。验证发现验证组患者0、20、40 Gy辐照后循环血miR-29a和miR-1 5 0表达具有统计学差异(P<0.05)。验证组循环miR-29a和miR-150分别与V5、V20、MLD、Mean Eso呈负相关。A549及MRC5细胞辐照3天后细胞内miR-29a和miR-150表达显著增加(P<0.05),细胞上清外泌体中表达显著下降(P<0.05)。结论:循环血miR-29a和miR-150与NSCLC胸部放射治疗剂量相关。
Objective: To investigate the correlation between circulating miR-29a and miR-150 and delivered dose during thoracic radiation therapy( RT) for non-small cell lung cancer( NSCLC). Methods: 56 cases of NSCLC patients who received radiotherapy in our hospital were collected from January,2014 to December,2015. miRNA profiling of plasma samples obtained from 5 NSCLC patients( miRNA array group) at 0,20,40,60 Gy each during radical thoracic RT by miRNA array. Candidate miRNAs were then assessed in samples from a separate cohort of 51 NSCLC patients( validation group) at 0,20,40 Gy each during receiving radical thoracic RT by qRT-PCR. qRT-PCR were used to identify cellular source of circulating miR-29a and miR-150 within intracellularly and secreted exosomes in A549 and MRC5 cells which received radiation treatment with 2 Gy/d for successive 3 days. Results: 10 miRNA( miR-29a,miR-150,miR-142,miR-342,miR-125b,miR-101,miR-425,miR-338,miR-126,miR-15 b)were screened out with the increase of RT dose in NSCLC patients. The results showed that there exists significant difference of the expression of circulating miR-29a and miR-150 in the validation group under 0,20,40 Gy radiation,respectively( P < 0. 05). The circulating miR-29a and miR-150 expression of the validation group were negatively correlated with V5,V20,mean lung dose( MLD),mean esophagus dose,respectively. The expression of miR-29a and miR-150 were increased significantly( P < 0. 05) after 3 days irradiation of A549 and MRC5 cells,meanwhile,decreased significantly( P < 0. 05) in secreted exosomes of A549 and MRC5 cells with radiation. Conclusion:Circulating miR-29a and miR-150 were correlated with NSCLC RT dose.
Objective: To investigate the correlation between circulating miR-29a and miR-150 and delivered dose during thoracic radiation therapy( RT) for non-small cell lung cancer( NSCLC). Methods: 56 cases of NSCLC patients who received radiotherapy in our hospital were collected from January,2014 to December,2015. miRNA profiling of plasma samples obtained from 5 NSCLC patients( miRNA array group) at 0,20,40,60 Gy each during radical thoracic RT by miRNA array. Candidate miRNAs were then assessed in samples from a separate cohort of 51 NSCLC patients( validation group) at 0,20,40 Gy each during receiving radical thoracic RT by qRT-PCR. qRT-PCR were used to identify cellular source of circulating miR-29a and miR-150 within intracellularly and secreted exosomes in A549 and MRC5 cells which received radiation treatment with 2 Gy/d for successive 3 days. Results: 10 miRNA( miR-29a,miR-150,miR-142,miR-342,miR-125b,miR-101,miR-425,miR-338,miR-126,miR-15 b)were screened out with the increase of RT dose in NSCLC patients. The results showed that there exists significant difference of the expression of circulating miR-29a and miR-150 in the validation group under 0,20,40 Gy radiation,respectively( P < 0. 05). The circulating miR-29a and miR-150 expression of the validation group were negatively correlated with V5,V20,mean lung dose( MLD),mean esophagus dose,respectively. The expression of miR-29a and miR-150 were increased significantly( P < 0. 05) after 3 days irradiation of A549 and MRC5 cells,meanwhile,decreased significantly( P < 0. 05) in secreted exosomes of A549 and MRC5 cells with radiation. Conclusion:Circulating miR-29a and miR-150 were correlated with NSCLC RT dose.
引文
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[15]Jiang XX,Liu Y,Li H,et al.MYSM1/miR-150/FLT3 inhibits B1a cell proliferation[J].Oncotarget,2016,7(42):68086-68096.
[2]Garg S,Gielda BT,Kiel K,et al.Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy[J].Pract Radiat Oncol,2014,4(5):342-348.
[3]Tabchi S,Blais N,Campeau MP,et al.Single-center comparison of multiple chemotherapy regimens for concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer[J].Cancer Chemother Pharmacol,2017,79(2):381-387.
[4]Tomasetti M,Lee W,Santarelli L,et al.Exosome-derived microRNAs in cancer metabolism:possible implications in cancer diagnostics and therapy[J].Exp Mol Med,2017,49(1):e285.
[5]Chen X,Xu Y,Liao X,et al.Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer[J].Tumour Biol,2016,37(9):11927-11936.
[6]Yoon SM,Shaikh T,Hallman M.Therapeutic management options for stage III non-small cell lung cancer[J].World J Clin Oncol,2017,8(1):1-20.
[7]Giridhar P,Mallick S,Rath GK,et al.Radiation induced lung injury:prediction,assessment and management[J].Asian Pac J Cancer Prev,2015,16(7):2613-2617.
[8]Sprung CN,Forrester HB,Siva S,et al.Immunological markers that predict radiation toxicity[J].Cancer Lett,2015,368(2):191-197.
[9]Wang Y,Liu J,Chen J,et al.MiR-29 mediates TGFβ1-induced extracellular matrix synthesis through activation of Wnt/β-catenin pathway in human pulmonary fibroblasts[J].Technol Health Care,2015,23 Suppl 1:S119-125.
[10]Cushing L,Kuang PP,Qian J,et al.miR-29 is a major regulator of genes associated with pulmonary fibrosis[J].Am J Respir Cell Mol Biol,2011,45(2):287-294.
[11]Xiao J,Meng XM,Huang XR,et al.miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice[J].Mol Ther,2012,20(6):1251-1260.
[12]Chen JS,Su YQ.Expression of miRNA-29s in non-small cell lung cancer and its clinical significance[J].Chin Clin Oncol,2016,21(12):1090-1095.[陈加顺,束永前.miR-29s在非小细胞肺癌组织中的表达及临床意义[J].临床肿瘤学杂志,2016,21(12):1090-1095.]
[13]Li YB,Lin LZ,Guan JS,et al.TCM combined western medicine treatment of advanced NSCLC[J].Chinese Journal of Integrated Traditional and Western Medicine,2016,36(9):1076-1082.[李元宾,林丽珠,关洁珊,等.中西医联合治疗对晚期NSCLC miRNA表达谱的影响[J].中国中西医结合杂志,2016,36(9):1076-1082.]
[14]Zeng XL,Zhang SY,Zheng JF,et al.Expression of microRNA-150 in peripheral blood and its clinical significance in patients with non-small cell lung cancer[J].Chin J Clinical Oncol,2012,39(22):1783-1787.[曾小莉,张韶岩,郑君芳,等.微小RNA-150在非小细胞肺癌外周血中的表达及其临床意义[J].中国肿瘤临床,2012,39(22):1783-1787.]
[15]Jiang XX,Liu Y,Li H,et al.MYSM1/miR-150/FLT3 inhibits B1a cell proliferation[J].Oncotarget,2016,7(42):68086-68096.