miR200家族在乳腺癌患者血浆中表达水平的检测及其临床意义

doi:10.13481/j.1671-587x.20190229

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (02): 383-388.doi: 10.13481/j.1671-587x.20190229

• 临床研究 • 上一篇

miR200家族在乳腺癌患者血浆中表达水平的检测及其临床意义

商琰红¹, 潘禹辰², 贾志芳², 王玥琦², 杨娜², 赵丹², 姜晶²

1. 河北大学附属医院肿瘤内科河北省肿瘤放化疗机制与规程研究重点实验室, 河北保定 071000;
2. 吉林大学第一医院临床研究部, 吉林长春 130021

收稿日期:2018-05-30 发布日期:2019-03-29
通讯作者: 姜晶,教授,博士研究生导师(Tel:0431-81875408,E-mail:jiangjing19702000@jlu.edu.cn) E-mail:jiangjing19702000@jlu.edu.cn
作者简介:商琰红(1973-),女,河北省保定市人,副主任医师,医学硕士,主要从事肿瘤内科胸部肿瘤方面的研究。
基金资助:
河北省卫计委医学科学研究重点课题计划项目资助课题（ZL20140335）；吉林省科技厅科技发展计划项目资助课题（20150414014GH）

Detection of expression levels of miR200 family in plasma of breast cancer patients and its significance

SHANG Yanhong¹, PAN Yuchen², JIA Zhifang², WANG Yueqi², YANG Na², ZHAO Dan², JIANG Jing²

1. Department of Medical Oncology, Affiliated Hospital, Hebei University, Key Laboratory of Cancer Radiotherapy of Hebei Province, Baoding 071000, China;
2. Department of Clinical Research, First Hospital, Jilin University, Changchun 130021, China

Received:2018-05-30 Published:2019-03-29

摘要/Abstract

摘要： 目的：检测microRNA200（miR200）家族在乳腺癌患者和正常人血浆中表达水平，评价其对乳腺癌筛查、进展和预后评估的潜在价值。方法：收集82例乳腺癌患者（乳腺癌组）和30名健康女性（对照组）的血浆标本，提取血浆中的微小RNAs （miRNAs），逆转录后采用实时荧光定量PCR法检测2组受试对象血浆中miR200家族（miR200a、miR200b、miR200c、miR141和miR429）的表达水平；采用受试者工作特征（ROC）曲线评价血浆中miRNAs的诊断价值，分析乳腺癌患者血浆miRNAs表达水平与临床病理参数的关系；采用Cox风险比例模型进行生存分析。结果：乳腺癌组患者血浆中miR141表达水平低于对照组（P<0.01），ROC曲线下面积（AUC）为0.717（P<0.01）；miR200b表达水平低于对照组（P=0.006），AUC为0.685（P=0.003）；但miR200a、miR200c和miR429表达水平与对照组比较差异无统计学意义（P=0.268，P=0.075，P=0.872）。联用miR141和miR200b时，AUC为0.735，比单用miR141稍有提升。miR200家族的表达水平与乳腺癌临床病理特征和术后总生存期无关联（P>0.05）。结论：miR200b和miR141有可能作为乳腺癌诊断的分子生物学指标。

关键词: 乳腺肿瘤, 微小RNAs, microRNA200家族, miR200a, miR200b, miR200c, miR141, miR429

Abstract: Objective: To detect the expression levels of microRNA200 (miR200) family in the plasma of the breast cancer patients and the normal controls, and to evaluate their potential values in the screening, progression and prognosis evaluation of breast cancer.Methods: A total of 82 cases of plasma samples of the patients with breast cancer (breast cancer group) and 30 cases of healthy plasma samples (control group) were collected.The microRNAs(miRNAs) were extracted from the plasma samples, the expression levels of miR200 family (miR200a, miR200b, miR200c, miR141 and miR429) were quantified by using real-time PCR technique.The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of miRNAs, and the associations between the levels of miRNAs and the clinicopathological characteristics were analyzed.Cox proportional hazard mode was used for survival analysis.Results: Compared with control group, the expression level of miR141 in the plasma of the patients in breast cancer group was decreased(P<0.01),and the area under the ROC curve (AUC) was 0.717(P<0.01); the expression level of miR200b was also decreased (P=0.006), the AUC was 0.685 (P= 0.003); the expression levels of miR200a, miR200c and miR429 had no significant differences between two groups(P=0.268, P=0.075, P=0.872). The AUC of combination of miR200b and miR141 was 0.735(P<0.01), the efficacy was superior to that of miR141 used alone. There were no statistically significant associations between the expression levels of miR200 family and the clinicopathological characteristics of breast cancer and postoperative overall survival(P>0.05).Conclusion: MiR200b and miR141 are likely to become the molecular biological parameters for the diagnosis of breast cancer.

Key words: breast neoplasms, microRNA, miR200, miR200a, miR200b, miR200c, miR141, miR429

中图分类号:

R737.9

商琰红, 潘禹辰, 贾志芳, 王玥琦, 杨娜, 赵丹, 姜晶. miR200家族在乳腺癌患者血浆中表达水平的检测及其临床意义[J]. 吉林大学学报(医学版), 2019, 45(02): 383-388.

SHANG Yanhong, PAN Yuchen, JIA Zhifang, WANG Yueqi, YANG Na, ZHAO Dan, JIANG Jing. Detection of expression levels of miR200 family in plasma of breast cancer patients and its significance[J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 383-388.

参考文献

[1] SIEGEL R L, MILLER K D, JEMAL A.Cancer statistics, 2015[J].CA Cancer J Clin, 2015, 65(1):5-29.
[2] ZUO T T, ZHENG R S, ZENG H M, et al.Female breast cancer incidence and mortality in China, 2013[J].Thorac Cancer, 2017, 8(3):214-218.
[3] CHEN W, ZHENG R, BAADE P D, et al.Cancer statistics in China, 2015[J].CA Cancer J Clin, 2016, 66(2):115-132.
[4] VOLINIA S, GALASSO M, SANA M E, et al.Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA[J].Proc Natl Acad Sci USA, 2012, 109(8):3024-3029.
[5] BLENKIRON C, GOLDSTEIN L D, THORNE N P, et al.MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype[J].Genome Biol, 2007, 8(10):R214.
[6] ZHENG R Z, LIU Y H, ZHANG X L, et al.miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest and targeting P21[J].Biomed Pharmacother, 2017, 90:517-523.
[7] BHARDWAJ M, SEN S, CHOSDOL K, et al.MiRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma[J].Br J Ophthalmol, 2017,101(4):536-542.
[8] KNUDSEN K N, LINDEBJERG J, NIELSEN B S, et al.MicroRNA-200b is downregulated in colon cancer budding cells[J].PLoS ONE, 2017, 12(5):e0178564.
[9] MING J,ZHOU Y,DU J Z, et al.Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells[J].Biosci Rep, 2015, 35(5):e00251.
[10] 石峰, 闫凤彩, 宋清坤, 等.MiR-200b及miR-200c在三阴性乳腺癌中的表达及意义[J].诊断病理学杂志, 2017, 24(12):926-929.
[11] 郑莹, 吴春晓, 张敏璐.乳腺癌在中国的流行状况和疾病特征[J].中国癌症杂志, 2013, 23(8):561-569.
[12] 柏尚柱.乳腺癌在中国的流行状况和疾病特征[J].世界最新医学信息文摘:电子版, 2017,17(41):253,256.
[13] MISKA E A.How microRNAs control cell division, differentiation and death[J].Curr Opin Genet Dev, 2005, 15(5):563-568.
[14] ILIOPOULOS D, LINDAHL-ALLEN M, POLYTARCHOU C, et al.Loss of miR-200 inhibition of Suz12 leads to Polycomb-mediated repression required for the formation and maintenance of cancer stem cells[J].Mol Cell, 2010, 39(5):761-772.
[15] LIM Y Y, WRIGHT J A, ATTEMA J L, et al.Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state[J].J Cell Sci, 2013, 126(Pt 10):2256-2266.
[16] UHLMANN S, ZHANG J D, SCHWÄGER A, et al.miR-200bc/429 cluster targets PLCγ1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer[J].Oncogene, 2010, 29(30):4297-4306.
[17] WELLNER U, SCHUBERT J, BURK U C, et al.The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs[J].Nat Cell Biol, 2009, 11(12):1487-1495.
[18] GREGORY P A, BERT A G, PATERSON E L, et al.The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1[J].Nat Cell Biol, 2008, 10(5):593-601.
[19] YE F, TANG H L, LIU Q, et al.MiR-200b as a prognostic factor in breast cancer targets multiple members of RAB family[J].J Transl Med, 2014, 12(1):1-10.
[20] ANTOLÍN S, CALVO L, BLANCO-CALVO M, et al.Circulating miR-200c and miR-141 and outcomes in patients with breast cancer[J].BMC Cancer, 2015, 15:297.

miR200家族在乳腺癌患者血浆中表达水平的检测及其临床意义

Detection of expression levels of miR200 family in plasma of breast cancer patients and its significance

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