miRNA-223和miRNA-155在非小细胞肺癌患者血浆中的表达研究
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摘要
目的探讨miRNA-223 (miR-223)、miRNA-155 (miR-155)在非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血浆中的表达。方法收集2014年1月至2016年6月在台州市第一人民医院住院的NSCLC患者87例(NSCLC组)及同期进行健康体检的30例(对照组)为研究对象,采用实时荧光定量RT-PCR (qRT-PCR)方法检测外周血浆中miR-223和miR-155水平,分析血浆中miR-223和miR-155表达量与各病理特征关系。结果血浆中miR-223和miR-155在NSCLC组表达水平高于对照组(t=5.083、7.496,P<0.05);miR-223和miR-155在NSCLC患者血浆中的表达水平与TNM分期有关(t=-4.682、-9.536,P<0.05),与性别、年龄、组织学类型、分化程度无关(P>0.05);miR-223诊断NSCLC的AUC为0.817,界值、敏感度、特异度、准确度、约登指数分别为0.305、70.11%、83.33%、73.50%和0.534;miR-155诊断NSCLC的AUC为0.901,界值、敏感度、特异度、准确度、约登指数分别为2.005、80.46%、90.00%、82.91%和0.705;miR-223和miR-155两者联合检测的敏感度、特异度和准确度为85.06%、83.33%和84.62%。miR-223和miR-155低表达组比高表达有更好的累积生存率(P<0.05)。结论 miR-223和miR-155在NSCLC患者血浆中的高表达提示其可作为NSCLC早期诊断的标志物,两者联合检测能提高诊断效能。
Objective To elucidate the expression of miRNA-223(miR-223)and miRNA-155(miR-155)in patients with non-small cell lung cancer(NSCLC). Methods 87 patients with NSCLC hospitalized in the first People′s Hospital of Taizhou from Jan.2014 to Jun.2016 and 30healthy controls were enrolled in this study.Blood samples were collected and the plasma levels of miR-223 and miR-155 were determined by realtime quantitative RT-PCR.The correlation of miR-223 and miR-155 levels in plasma with clinical and pathological features was analyzed. Results The expression levels of miR-223 and miR-155 were significantly higher among patients with NSCLC compared to controls(t=5.083,7.496,P<0.05).The expression levels of miR-223 and miR-155 in plasma of NSCLC patients were correlated with TNM stage(t=4.682,-9.536,P<0.05),but not with gender,age,histological type and differentiation degree(P>0.05).The AUC,cutoff,sensitivity,specificity,accuracy and Jorden index were 0.817,0.305,70.11%,83.33%,73.50%,0.534 for miR-223 and were 0.901,2.005,80.46%,90.00%,82.91%and 0.705 for miR-155 in the diagnosis of NLCLC.The sensitivity,specificity and accuracy of joint detection of miR-223 and miR-155 in the diagnosis of NSCLC were 85.06%,83.33% and 84.62%.The accumulated survival rate of patients with lower plasma levels of miR-223 and miR-155 was significantly higher than those with higher levels(P<0.05).Conclusions The high expression of miR-223 and miR-155 in plasma of patients with NSCLC suggests that it can be used as a marker for the early diagnosis of NSCLC,and joint detection of both can improve the diagnostic efficiency.
Objective To elucidate the expression of miRNA-223(miR-223)and miRNA-155(miR-155)in patients with non-small cell lung cancer(NSCLC). Methods 87 patients with NSCLC hospitalized in the first People′s Hospital of Taizhou from Jan.2014 to Jun.2016 and 30healthy controls were enrolled in this study.Blood samples were collected and the plasma levels of miR-223 and miR-155 were determined by realtime quantitative RT-PCR.The correlation of miR-223 and miR-155 levels in plasma with clinical and pathological features was analyzed. Results The expression levels of miR-223 and miR-155 were significantly higher among patients with NSCLC compared to controls(t=5.083,7.496,P<0.05).The expression levels of miR-223 and miR-155 in plasma of NSCLC patients were correlated with TNM stage(t=4.682,-9.536,P<0.05),but not with gender,age,histological type and differentiation degree(P>0.05).The AUC,cutoff,sensitivity,specificity,accuracy and Jorden index were 0.817,0.305,70.11%,83.33%,73.50%,0.534 for miR-223 and were 0.901,2.005,80.46%,90.00%,82.91%and 0.705 for miR-155 in the diagnosis of NLCLC.The sensitivity,specificity and accuracy of joint detection of miR-223 and miR-155 in the diagnosis of NSCLC were 85.06%,83.33% and 84.62%.The accumulated survival rate of patients with lower plasma levels of miR-223 and miR-155 was significantly higher than those with higher levels(P<0.05).Conclusions The high expression of miR-223 and miR-155 in plasma of patients with NSCLC suggests that it can be used as a marker for the early diagnosis of NSCLC,and joint detection of both can improve the diagnostic efficiency.
引文
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[16] Ma J,Fang B,Zeng F,et al.Down-regulation of miR-223reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells[J].Oncotarget,2015,6(3):1740-1749.
[17]胡敏,魏晓霞,邹杰,等.miRNA-223对非小细胞肺癌A549/DDP细胞顺铂耐药性的影响[J].临床肿瘤学杂志,2015,20(5):411-416.
[18] Pang W,Su J,Wang Y,et al.Pancreatic cancer-secreted miR-155implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts[J].Cancer Sci,2015,106(10):1362-1369.
[19] Lantermann AB,Chen D,McCutcheon K,et al.Inhibition of casein kinase 1alpha prevents acquired drug resistance to erlotinib in EGFR-mutant non-small cell lung cancer[J].Cancer Res,2015,75(22):4937-4948.
[20] Vincenzi B,Iuliani M,Zoccoli A,et al.Deregulation of dicer and mir-155expression in liposarcoma[J].Oncotarget,2015,6(12):10586-10591.
[21]戴斌,杨颖乔,黄翠萍.miR-133b与miR-155在非小细胞肺癌患者肿瘤及周围组织中的表达及意义[J].基因组学与应用生物学,2017,36(5):1702-1708.
[22] Yang M,Shen H,Qiu C,et al.High expression of miR-21and miR-155predicts recurrence and unfavourable survival in non-small cell lung cancer[J].Eur J Cancer,2013,49(3):604-615.
[23]高轶,付圣灵,江文洋,等.pⅢ期非小细胞肺癌中miR-155的表达与预后关系的研究[J].中国肺癌杂志,2014,17(5):417-423.
[2] Pitman S,Cho KH.The mechanisms of virulence regulation by small noncoding RNAs in low GC gram-positive pathogens[J].Int J Mol Sci,2015,16(12):29797-29814.
[3] Siegel R,DeSantis C,Virgo K,et al.Cancer treatment and survivorship statistics,2012[J].CA Cancer J Clin,2012,62(4):220-241.
[4]杨健,张秀伟,文昱婷,等.miR-155在非小细胞肺癌患者血清中的表达及其临床意义[J].实用老年医学,2012,26(6):459-461.
[5] Kasinski AL,Kelnar K,Stahlhut C,et al.A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer[J].Oncogene,2015,34(27):3547-3555.
[6] Chen Z,Jin Y,Yu D,et al.Down-regulation of the microRNA-99family members in head and neck squamous cell carcinoma[J].Oral Oncol,2012,48(8):686-691.
[7] Eto K,Iwatsuki M,Watanabe M,et al.The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7pathway[J].Int J Cancer,2015,136(7):1537-1545.
[8] Chen X,Hu Z,Wang W,et al.Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis[J].Int J Cancer,2012,130(7):1620-1628.
[9] Shibuya H,Nakasa T,Adachi N,et al.Overexpression of microRNA-223in rheumatoid arthritis synovium controls osteoclast differentiation[J].Mod Rheumatol, 2013,23(4):674-685.
[10]Wu C,Li M,Hu C,et al.Clinical significance of serum miR-223,miR-25and miR-375in patients with esophageal squamous cell carcinoma[J].Mol Biol Rep,2014,41(3):1257-1266.
[11] Dong YW,Wang R,Cai QQ,et al.Sulfatide epigenetically regulates miR-223and promotes the migration of human hepatocellular carcinoma cells[J].J Hepatol,2014,60(4):792-801.
[12] Ma L,Chen Y,Zhang B,et al.Increased microRNA-223in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration[J].Biosci Biotechnol Biochem,2014,78(4):602-608.
[13]郭玉庆,张建华,郭玉双.miR-223通过靶定EPB41L3促进胃癌生长和侵袭的研究[J].哈尔滨医科大学学报,2014,48(5):381-385.
[14]牛少曦,马鑫,张瑜,等.miR-223在肾透明细胞癌中的表达与功能[J].南方医科大学学报,2015,35(3):338-342.
[15]王云雀,黄湘壹.MicroRNA-223表达与肝癌根治性切除术预后的相关性[J].中国现代医学杂志,2017,27(6):59-64.
[16] Ma J,Fang B,Zeng F,et al.Down-regulation of miR-223reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells[J].Oncotarget,2015,6(3):1740-1749.
[17]胡敏,魏晓霞,邹杰,等.miRNA-223对非小细胞肺癌A549/DDP细胞顺铂耐药性的影响[J].临床肿瘤学杂志,2015,20(5):411-416.
[18] Pang W,Su J,Wang Y,et al.Pancreatic cancer-secreted miR-155implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts[J].Cancer Sci,2015,106(10):1362-1369.
[19] Lantermann AB,Chen D,McCutcheon K,et al.Inhibition of casein kinase 1alpha prevents acquired drug resistance to erlotinib in EGFR-mutant non-small cell lung cancer[J].Cancer Res,2015,75(22):4937-4948.
[20] Vincenzi B,Iuliani M,Zoccoli A,et al.Deregulation of dicer and mir-155expression in liposarcoma[J].Oncotarget,2015,6(12):10586-10591.
[21]戴斌,杨颖乔,黄翠萍.miR-133b与miR-155在非小细胞肺癌患者肿瘤及周围组织中的表达及意义[J].基因组学与应用生物学,2017,36(5):1702-1708.
[22] Yang M,Shen H,Qiu C,et al.High expression of miR-21and miR-155predicts recurrence and unfavourable survival in non-small cell lung cancer[J].Eur J Cancer,2013,49(3):604-615.
[23]高轶,付圣灵,江文洋,等.pⅢ期非小细胞肺癌中miR-155的表达与预后关系的研究[J].中国肺癌杂志,2014,17(5):417-423.
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