血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值

doi:10.6040/j.issn.1671-7554.0.2017.111

摘要/Abstract

摘要： 目的检测miR-17-92簇成员分子(miR-17、miR-18a、miR-19a、miR-19b、miR-20a和miR-92a)在人乳头瘤病毒(HPV)阳性宫颈癌(CC)及上皮内瘤变(CIN)患者血清中的表达水平,并评估其对HPV阳性宫颈癌的早期诊断价值。方法收集HPV阳性宫颈癌患者150例(CC组)、HPV阳性CIN1~3级患者100例(CIN组)及单纯HPV阳性或子宫良性病变者150例(对照组)血清,采用实时定量PCR(RT-qPCR)法检测血清中miR-17-92簇成员分子的表达,结合液基薄层细胞学检测(TCT)结果,评价miR-17-92簇成员分子在HPV阳性宫颈癌中的早期诊断价值。结果与对照组相比,miR-18a和miR-92a在CC组血清中异常高表达,且其表达水平显著高于CIN组及对照组,两者在CIN3级患者中的表达水平及miR-18a在CIN1-2级患者中的表达水平均显著高于对照组(P均<0.05)。受试者工作曲线(ROC曲线)分析结果显示,血清miR-18a诊断CIN3及CC(CIN3+)的曲线下面积(AUC)为0.792(95%CI:0.749~0.862),灵敏度为87%,特异度为65%;血清miR-92a诊断CIN3+的AUC为0.799(95%CI:0.744~0.847),灵敏度为55.8%,特异度为92%;TCT诊断CIN3+的AUC为0.645(95%CI:0.582~0.704),灵敏度为51.9%,特异度为77%。血清miR-18a和miR-92对宫颈癌和CIN3+的诊断效能均显著优于TCT检测(P均<0.01)。结论 miR-17-92簇成员分子miR-92a和miR-18a在HPV阳性宫颈癌患者血清中高表达,并可作为HPV阳性宫颈癌的早期诊断及鉴别高级别CIN的潜在标志物。

关键词: 宫颈癌, 宫颈上皮内瘤变, miR-17-92簇, 人乳头瘤病毒, 血清

Abstract: Objective To detect the expression levels of miR-17-92 cluster(miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a)in the serum from patients with cervical cancer(CC)and cervical intraepithelial neoplasia(CIN), and to evaluate their clinical significance in the early diagnosis of human papillomavirus(HPV)positive cervical cancer. Methods Serum samples were collected from 150 HPV positive CC patients(cancer group), 100 HPV-positive patients with CIN1-3(CIN group)and 50 HPV-positive women without malignant disease(control group). RT-qPCR was performed to analyze the expression levels of serum miR-17-92 cluster. The diagnostic values of the differently expressed miRNAs were evaluated and compared with Thinprep cytologic test(TCT). Results The expression 山东大学学报 (医学版)55卷5期 -刘京康,等.血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值 \=-of serum miR-18a and miR-92a were significantly higher in CC group than in CIN group and control group; the expression of serum miR-18a and miR-92a were significantly higher in CIN group than in control group; the expression of miR-18a was significantly higher in CIN1-2 patients than in control group(all P<0.05). Receiver operating characteristic(ROC)curve analysis revealed that the area under the curve(AUC)of serum miR-18a, miR-92a and TCT for identifying CIN3 and CC(CIN3+)was 0.792(95%CI: 0.749-0.862; sensitivity: 87%; specificity: 65%), 0.799(95%CI: 0.744-0.847; sensitivity: 55.8%; specificity: 92%)and 0.645(95%CI: 0.582-0.704; sensitivity: 51.9%; specificity: 77%), respectively. Compared with TCT, detection of serum miR-18a and miR-92a achieved higher performance efficiency for identifying CIN3+(all P<0.01). Conclusion MiR-18a and miR-92a, the members of miR-17-92 cluster, are highly expressed in the serum of HPV-positive patients with cervical cancer, and could serve as potential biomarkers for early diagnosis of cervical neoplasia and high-grade CIN identification.

Key words: Cervical cancer, Cervical intraepithelial neoplasia, MiR-17-92 cluster, Human papillomavirus, Serum

中图分类号:

R711

刘京康,杨建勇,孟丽华,姜洁. 血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值[J]. 山东大学学报（医学版）, 2017, 55(5): 86-90.

LIU Jingkang, YANG Jianyong, MENG Lihua, JIANG Jie. The value of serum miR-17-92 cluster in early diagnosis of HPV-positive cervical cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 86-90.

参考文献

[1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1): 7-30.
[2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[3] He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene[J]. Nature, 2005, 435(7043): 828-833.
[4] 姚烜, 张灵敏, 汪洋, 等. miR-17-92基因簇反义寡核苷酸对胃癌细胞增殖与侵袭的抑制作用[J]. 现代肿瘤医学, 2011, 19(5): 852-855. YAO Xuan, ZHANG Lingmin, WANG Yang, et al. Effect of miR-17-92 cluster on proliferation and metastasis of human gastric cancer cell line SGC-7901[J]. Modern Oncology, 2011, 19(5): 852-855.
[5] Ke TW, Wei PL, Yeh KT, et al. MiR-92a promotes cell metastasis of colorectal cancer through PTEN-Mediated PI3K/AKT pathway[J]. Ann Surg Oncol, 2015, 22(8): 2649-2655.
[6] Honegger A, Schilling D, Bastian S, et al. Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells[J]. PLoS Pathog, 2015, 11(3): 1004712.
[7] Naucler P, Ryd W, Törnberg S, et al. Human papillomavirus and papanicolaou tests to screen for cervical cancer[J]. N Engl J Med, 2007, 357(16): 1589-1597.
[8] Kitchener HC, Almonte M, Thomson C, et al. HPV testing in combina -tion with liquid-based cytology in primary cervical screening(ARTISTIC): a randomised controlled trial[J]. Lancet Oncol, 2009, 10(7): 672-682.
[9] Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavi-rus DNA versus Papanicolaou screening tests for cervical cancer[J]. N Engl J Med, 2007, 357(16): 1579-1588.
[10] Ronco G, Giorgi-Rossi P, Carozzi F, et al. Efficacy of human papillo -mavirus testing for the detection of invasive cervical cancers and cervi-cal intraepithelial neoplasia: a randomised controlled trial[J]. Lancet Oncol, 2010, 11(3): 249-257.
[11] Whitlock EP, Vesco KK, Eder M, et al. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a system -atic review for the U.S. Preventive Services Task Force[J]. Ann Intern Med, 2011, 155(10): 687-697.
[12] 李红, 李铤, 刘常浩, 等.循环血清miR-17-92簇: 一种新的胃癌诊断标志物[J]. 现代肿瘤医学, 2014, 22(3): 581-585. LI Hong, LI Ting, LIU Changhao, et al. Circulating miR-17-92 cluster in serum: novel potential biomarkers for gastric cancer[J]. Modern Oncology, 2014, 22(3): 581-585.
[13] Puerta-Gil P, Garcia-Baquero R, Jia AY, et al. miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer[J]. Am J Pathol, 2012,180(5): 1808-1815.
[14] Cui L, Zhang X, Ye G, et al. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer[J]. Cancer, 2013, 119(9): 1618-1626.
[15] 徐臣光, 陈静, 许践刚, 等. 血清miRNA作为结直肠癌患者诊断标志物的价值研究[J].肿瘤学杂志, 2015, 21(5): 405-410. XU Chenguang, CHEN Jing, XU Jiangang, et al. Study on the role of serum microRNA as diagnostic biomarker for colorectal cancer patients[J]. Journal of Chinese Oncology, 2015, 21(5): 405-410.
[16] Wang X, Wang HK, Li Y, et al. MicroRNAs are biomarkers of oncogenic human papillomavirus infections[J]. Proc Natl Acad Sci U S A, 2014, 111(11): 4262-4267.
[17] Su Z, Yang H, Zhao M, et al. MicroRNA-92a Promotes cell proliferation in cervical cancer via inhibiting p21 expression and promoting cell cycle progression[J]. Oncol Res, 2017, 25(1): 137-145.
[18] Zhou C, Shen L, Mao L, et al. MiR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7[J]. Biochem Biophys Res Commun, 2015, 458(1): 63-69.
[19] Chiantore MV, Mangino G, Iuliano M, et al. Human papillomavirus E6 and E7 oncoproteins affect the expression of cancer-related microRNAs: additional evidence in HPV-induced tumorigenesis[J]. J Cancer Res Clin Oncol, 2016, 142(8): 1751-1763.
[20] Kong Q, Tang Z, Xiang F, et al. Diagnostic Value of serum hsa-mir-92a in patients with cervical cancer[J]. Clinical Laboratory, 2017, 63(2): 335-340.

相关文章 15

[1]	李波波李道堂刘曙光王兴武. 食管癌患者血清中DKK-1的表达[J]. 山东大学学报(医学版), 2209, 47(6): 58-61.
[2]	张辉时庆侯怀水李栋. 人脐带间充质干细胞的无动物血清培养及向肝细胞诱导分化[J]. 山东大学学报(医学版), 2209, 47(6): 88-.
[3]	李宁张征张宏群高希宝. 济南居民膳食硒摄入量与血清硒参考值调查[J]. 山东大学学报(医学版), 2209, 47(6): 121-122.
[4]	张媛李英敏冯月秋常彩云潘华伟王束玫. 血清脂联素水平与肥胖、胰岛素抵抗的关系探讨[J]. 山东大学学报(医学版), 2209, 47(6): 124-.
[5]	孙泽雨,陈颖,林家香,刘娟,赵蔚明. 磷脂酰肌醇-4-磷酸酶II型对宫颈癌细胞增殖及凋亡的影响[J]. 山东大学学报（医学版）, 2017, 55(11): 1-6.
[6]	王雅芬,杨勇霞,刘娅,马德美,朱琳. 宫颈细胞学阴性且高危型人乳头瘤病毒阳性人群的分流方法[J]. 山东大学学报（医学版）, 2016, 54(8): 69-71.
[7]	林栋,管庆波. 2型糖尿病男性患者血清睾酮水平低下对非酒精性脂肪肝的影响[J]. 山东大学学报（医学版）, 2016, 54(7): 33-37.
[8]	马琳,张冬,唐蕾,叶嗣源,焉传祝,曹丽丽. 肌萎缩侧索硬化预后相关的血液学标志物[J]. 山东大学学报（医学版）, 2016, 54(4): 46-50.
[9]	彭慧,何君梅,苏雪莲. 血清循环miR-375检测对宫颈癌早期诊断及术后监测的意义[J]. 山东大学学报（医学版）, 2016, 54(3): 68-71.
[10]	张振堂,方立竹,薛在峰,赵丽,马东强,温红玲,刘建伟,张笑爽,于学杰. 2012年3月~2013年2月青岛市黄岛区肾综合征出血热流行特征[J]. 山东大学学报（医学版）, 2016, 54(11): 82-86.
[11]	宓特,屈传强,王翔,尹苓,薛媛,杜怡峰. 血清淀粉样蛋白A与脑梗死急性期认知功能的相关性[J]. 山东大学学报（医学版）, 2016, 54(10): 40-45.
[12]	田馨莉, 矫俊, 张腾, 马道新, 崔保霞. Th22细胞联合Th17细胞在宫颈癌外周血中的表达及意义[J]. 山东大学学报（医学版）, 2015, 53(7): 43-47.
[13]	方茜, 曲爱林, 张欣, 杜鲁涛, 杨咏梅, 王传新. 血清miR-210在结直肠癌患者血清中的表达及临床意义[J]. 山东大学学报（医学版）, 2015, 53(6): 77-81.
[14]	张荣军, 韩波, 高聆, 朱梅, 丁国玉, 梁燕. siRNA沉默CD40基因对实验性自身免疫性心肌炎大鼠的作用及IL-22表达的影响[J]. 山东大学学报（医学版）, 2015, 53(5): 36-40.
[15]	于磊, 李振. 白细胞介素33在脑血管病患者血清中的表达及其作用机制[J]. 山东大学学报（医学版）, 2015, 53(4): 75-79.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed