血清miR-210和miR-375在非小细胞肺癌患者中的表达变化情况
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摘要
目的探讨血清miR-210和miR-375在非小细胞肺癌(NSCLC)患者中的表达变化情况。方法以25例NSCLC患者(NSCLC组)和14例健康志愿者(对照组)为研究对象,随机抽取6例NSCLC组和6例对照组的血液标本组成筛选实验,应用实时荧光定量PCR(RT-qPCR)检测9种miRNA (miR-182、miR-126、miR-31、miR-21、miR-221、miR-200b、miR-183、miR-210、miR-375)的表达水平,筛选出表达异常的miRNA为目标miRNA后,继续检测其在剩余标本中的表达水平,并采用受试者工作特征曲线(ROC曲线)评价其诊断效能。结果筛选实验发现,miR-210和miR-375在NSCLC组血清中的相对表达均升高,差异有统计学意义(P<0.05),其他7种miRNA表达量趋势与已报道文献不符,选择miR-210和miR-375继续验证剩余标本,发现NSCLC患者中的肺腺癌组miR-210相对表达量较对照组升高,差异有统计学意义(P<0.05),肺鳞癌组与对照组比较,差异无统计学意义(P>0.05);miR-375在肺鳞癌和肺腺癌组中的相对表达量与对照组比较,差异均无统计学意义(P>0.05)。根据血清miR-210表达水平绘制ROC曲线,曲线下面积为0.737 5(95%CI:0.498 3～0.976 7,P=0.091 4),诊断准确性中等。结论 miR-210在肺腺癌组高表达,可能成为诊断肺腺癌的新型肿瘤标志物;miR-375在辅助诊断肺癌的价值仍待进一步探讨。
Objective To investigate the expression levels of serum miR-210 and miR-375 in patients with non-small cell lung cancer(NSCLC).Methods A total of 25 NSCLC patients(NSCLC group)and 14 healthy volunteers(control group)were enrolled in this study.The relative expression levels of 9 miRNAs(miR-182,miR-126,miR-31,miR-21,miR-221,miR-200 b,miR-183,miR-210 and miR-375)in 6 NSCLC patients and 6 healthy volunteers were measured by RT-qPCR.The dysregulated miRNAs will be selected as candidate miRNAs.The diagnostic value were evaluated by ROC curve.Results Compared with control group,2(miR-210 and miR-375)out of 9 miRNAs were up-regulated in NSCLC group,and the differences were statistically significant(P<0.05),while the other 7 miRNAs were not consistent with the reported literatures.Therefore,miR-210 and miR-375 were selected as candidate miRNAs.We found that the relative expression level of miR-210 in the lung adenocarcinoma group was significantly different from control group(P<0.05),while there was no significant difference between the squamous cell carcinoma group and the control group(P>0.05).There was no significantly statistical difference in the relative expression level of miR-375 between lung squamous cell carcinoma group,lung adenocarcinoma group and the control group(P>0.05).The AUC of serum miR-210 of lung adenocarcinoma group was 0.737 5(95%CI:0.498 3-0.976 7,P=0.091 4)with a medium diagnostic value.Conclusion MiR-210 is highly expressed in the serum of patients with lung adenocarcinoma,suggesting that miR-210 may be a novel tumor marker for the diagnosis of lung adenocarcinoma.The value of miR-375 in the diagnosis of lung cancer still needs to be further explored.
Objective To investigate the expression levels of serum miR-210 and miR-375 in patients with non-small cell lung cancer(NSCLC).Methods A total of 25 NSCLC patients(NSCLC group)and 14 healthy volunteers(control group)were enrolled in this study.The relative expression levels of 9 miRNAs(miR-182,miR-126,miR-31,miR-21,miR-221,miR-200 b,miR-183,miR-210 and miR-375)in 6 NSCLC patients and 6 healthy volunteers were measured by RT-qPCR.The dysregulated miRNAs will be selected as candidate miRNAs.The diagnostic value were evaluated by ROC curve.Results Compared with control group,2(miR-210 and miR-375)out of 9 miRNAs were up-regulated in NSCLC group,and the differences were statistically significant(P<0.05),while the other 7 miRNAs were not consistent with the reported literatures.Therefore,miR-210 and miR-375 were selected as candidate miRNAs.We found that the relative expression level of miR-210 in the lung adenocarcinoma group was significantly different from control group(P<0.05),while there was no significant difference between the squamous cell carcinoma group and the control group(P>0.05).There was no significantly statistical difference in the relative expression level of miR-375 between lung squamous cell carcinoma group,lung adenocarcinoma group and the control group(P>0.05).The AUC of serum miR-210 of lung adenocarcinoma group was 0.737 5(95%CI:0.498 3-0.976 7,P=0.091 4)with a medium diagnostic value.Conclusion MiR-210 is highly expressed in the serum of patients with lung adenocarcinoma,suggesting that miR-210 may be a novel tumor marker for the diagnosis of lung adenocarcinoma.The value of miR-375 in the diagnosis of lung cancer still needs to be further explored.
引文
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[24]ARAB A,KARIMIPOOR M,IRANI S,et al.Potential circulating miRNA signature for early detection of NSCLC[J].Cancer Genet,2017(216/217):150-158.
[25]ZHOU X,WEN W,SHAN X,et al.A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis[J].Oncotarget,2017,8(4):6513-6525.
[26]HALVORSEN A R,BJAANAES M,LEBLANC M,et al.A unique set of 6circulating microRNAs for early detection of non-small cell lung cancer[J].Oncotarget,2016,7(24):37250-37259.
[27]ZAPOROZHCHENKO I A,MOROZKIN E S,SKVORT SOVA T E,et al.Plasma miR-19band miR-183as potential biomarkers of lung cancer[J].PLoS One,2016,11(10):e0165261.
[28]RAMALINGAM S S,YANG J C,LEE C K,et al.Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer[J].J Clin Oncol,2018,36(9):841-849.
[29]MASAOUTIS C,MIHAILIDOU C,TSOUROUFLIS G,et al.Exosomes in lung cancer diagnosis and treatment.From the translating research into future clinical practice[J].Biochimie,2018,151:27-36.
[30]LUO H,GE H,CUI Y,et al.Systemic inflammation biomarkers predict survival in patients of early stage nonsmall cell lung cancer treated with stereotactic ablative radiotherapy:a single center experience[J].J Cancer,2018,9(1):182-188.
[31]GARCA-GIMNEZ J L,RUBIO-BELMAR P A,PEIR-CHOVA L,et al.Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis[J].Sci Rep,2018,8(1):2646.
[32]LOPEZ-SANTILLAN M,LARRABEITI-ETXEBARRIA A,ARZUAGA-MENDEZ J,et al.Circulating miRNAs as biomarkers in diffuse large B-cell lymphoma:a systematic review[J].Oncotarget,2018,9(32):22850-22861.
[2] CHEN W Q,ZHENG R S,BAADE P D,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3] OSMANI L,ASKIN F,GABRIELSON E,et al.Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma(NSCLC):moving from targeted therapy to immunotherapy[J].Semin Cancer Biol,2018,52(Pt 1):103-109.
[4] MACDONALD I K,PARSY-KOWALSKA C B,CHAPMAN C J.Autoantibodies:opportunities for early cancer detection[J].Trends Cancer,2017,3(3):198-213.
[5] SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[6] KUANG X Y,WEI C M,ZHANG T,et al.miR-378inhibits cell growth and enhances apoptosis in human myelodysplastic syndromes[J].Int J Oncol,2016,49(5):1921-1930.
[7] LENG Q X,WANG Y,JIANG F.A direct plasma miRNA assay for early detection and histological classification of lung cancer[J].Transl Oncol,2018,11(4):883-889.
[8] LI W D,LIU Y J,YANG W N,et al.MicroRNA-378enhances radiation response in ectopic and orthotopic implantation models of glioblastoma[J].J Neurooncol,2018,136(1):63-71.
[9] SHISHODIA G,VERMA G,DAS B C,et al.miRNA as viral transcription tuners in HPV-mediated cervical carcinogenesis[J].Front Biosci(Schol Ed),2018,10(1):21-47.
[10]LI J H,SUN S S,FU C J,et al.Diagnostic and prognostic value of microRNA-628for cancers[J].J Cancer,2018,9(9):1623-1634.
[11]HO C S,NOOR S M,NAGOOR N H.MiR-378and MiR-1827regulate tumor invasion,migration and angiogenesis in human lung adenocarcinoma by targeting RBX1and CRKL,respectively[J].J Cancer,2018,9(2):331-345.
[12]WU Y,ZHANG J,HONG Y,et al.Effects of kanglaite injection on serum miRNA-21in patients with advanced lung cancer[J].Med Sci Monit,2018,24:2901-2906.
[13]XU J,XIAO X,YANG D.In vitro methods for analyzing miRNA roles in cancer cell proliferation,invasion,and metastasis[J].Methods Mol Biol,2018,1733:159-171.
[14]MOTAWI T K,RIZK S M,IBRAHIM T M,et al.Circulating microRNAs,miR-92a,miR-100and miR-143,as non-invasive biomarkers for bladder cancer diagnosis[J].Cell Biochem Funct,2016,34(3):142-148.
[15]朱利群,王纯,陈菊香.血清miRNA-200b在非小细胞肺癌中的表达及其临床意义[J].实用癌症杂志,2017,32(7):1059-1061.
[16]SUN Y L,HAWKINS P G,BI N,et al.Serum microRNA signature predicts response to high-dose radiation therapy in locally advanced non-small cell lung cancer[J].Int J Radiat Oncol Biol Phys,2018,100(1):107-114.
[17]HALVORSEN A R,BJAANAES M,LEBLANC M,et al.A unique set of 6circulating microRNAs for early detection of non-small cell lung cancer[J].Oncotarget,2016,7(24):37250-37259.
[18]CASTILLO-LARA R A,SORIA-RUIZ M,MARTINEZCARRERA O.American college of chest physicians/society of critical care medicine consensus conference:definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis[J].Crit Care Med,1992,20(6):864-874.
[19]DETTERBECK F C,BOFFA D J,TANOUE L T.The new lung cancer staging system[J].Chest,2009,136(1):260-271.
[20]ZHU W,ZHOU K,ZHA Y,et al.Diagnostic value of serum miR-182,miR-183,miR-210,and miR-126levels in patients with early-stage non-small cell lung cancer[J].PLoS One,2016,11(4):e0153046.
[21]GRIMOLIZZI F,MONACO F,LEONI F,et al.Exosomal miR-126as a circulating biomarker in non-small-cell lung cancer regulating cancer progression[J].Sci Rep,2017,7(1):15277.
[22]MATHE Y G,FOGEL P,MARTIN L S,et al.60Pcirculating miR-31as a predictive marker of EGFR TKI treatment efficacy in squamous cell lung cancer(SCC):a sub-analysis of the LUX-Lung 8trial[J].J Thorac Oncol,2018,13(4):31-32.
[23]YANG Y,CHEN K,ZHOU Y,et al.Application of serum microRNA-9-5p,21-5p,and 223-3p combined with tumor markers in the diagnosis of non-small-cell lung cancer in Yunnan in southwestern China[J].Onco Targets Ther,2018,11:587-597.
[24]ARAB A,KARIMIPOOR M,IRANI S,et al.Potential circulating miRNA signature for early detection of NSCLC[J].Cancer Genet,2017(216/217):150-158.
[25]ZHOU X,WEN W,SHAN X,et al.A six-microRNA panel in plasma was identified as a potential biomarker for lung adenocarcinoma diagnosis[J].Oncotarget,2017,8(4):6513-6525.
[26]HALVORSEN A R,BJAANAES M,LEBLANC M,et al.A unique set of 6circulating microRNAs for early detection of non-small cell lung cancer[J].Oncotarget,2016,7(24):37250-37259.
[27]ZAPOROZHCHENKO I A,MOROZKIN E S,SKVORT SOVA T E,et al.Plasma miR-19band miR-183as potential biomarkers of lung cancer[J].PLoS One,2016,11(10):e0165261.
[28]RAMALINGAM S S,YANG J C,LEE C K,et al.Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer[J].J Clin Oncol,2018,36(9):841-849.
[29]MASAOUTIS C,MIHAILIDOU C,TSOUROUFLIS G,et al.Exosomes in lung cancer diagnosis and treatment.From the translating research into future clinical practice[J].Biochimie,2018,151:27-36.
[30]LUO H,GE H,CUI Y,et al.Systemic inflammation biomarkers predict survival in patients of early stage nonsmall cell lung cancer treated with stereotactic ablative radiotherapy:a single center experience[J].J Cancer,2018,9(1):182-188.
[31]GARCA-GIMNEZ J L,RUBIO-BELMAR P A,PEIR-CHOVA L,et al.Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis[J].Sci Rep,2018,8(1):2646.
[32]LOPEZ-SANTILLAN M,LARRABEITI-ETXEBARRIA A,ARZUAGA-MENDEZ J,et al.Circulating miRNAs as biomarkers in diffuse large B-cell lymphoma:a systematic review[J].Oncotarget,2018,9(32):22850-22861.