目的：研究宫颈癌患者血清miR-574-5p和miR-497-5p表达的临床意义。方法：选择2016年1月至2018年12月在我院诊治的宫颈癌患者116例，为宫颈癌组；选择同期在我院病理确诊为宫颈上皮内瘤变患者45例，为宫颈上皮内瘤变组；选择同期在我院行健康体检者30例，为健康对照组。运用实时荧光定量PCR方法检测各组血清miR-574-5p和miR-497-5p表达。观察各组入院时和宫颈癌术后血清miR-574-5p和miR-497-5p的表达水平，分析宫颈癌患者miR-574-5p和miR-497-5p表达水平与临床病理因素的关系，及两者的相关性。同时利用TCGA数据库中宫颈癌数据对miR-574-5p和miR-497-5p结合临床信息进行分析，最后基于miR-574-5p和miR-497-5p表达的风险分数预测患者预后。结果：宫颈癌组患者术前血清miR-574-5p表达水平明显高于宫颈上皮内瘤变组和健康对照组（P<0.01），且宫颈癌患者术后血清miR-574-5p表达水平较术前明显降低（P<0.01），而宫颈上皮内瘤变组术前明显高于健康对照组（P<0.01）；宫颈癌组患者术前血清miR-497-5p表达水平明显低于宫颈上皮内瘤变组和健康对照组（P<0.01），宫颈癌患者术后血清miR-497-5p表达水平较术前明显升高（P<0.01），而宫颈上皮内瘤变组术前明显低于健康对照组（P<0.01）。宫颈癌患者血清miR-574-5p和miR-497-5p表达水平与年龄、肿瘤类型、肿瘤大小及神经浸润无明显的相关性（P>0.05），而与肿瘤分化程度、FIGO分期、淋巴结转移和CA125水平具有明显相关性（P<0.01）。宫颈癌患者血清miR-574-5p表达水平与miR-497-5p表达水平呈负相关（r=-0.768，P<0.01）。进一步将miR-574-5p和miR-497-5p表达情况在TCGA数据库中进行验证，我院患者表达情况与之结果一致。并且在TCGA数据库中miR-574-5p表达与其肿瘤T分期进展呈正相关，与患者总生存时间（OS）呈负相关；miR-497-5p表达与其肿瘤T分期进展负相关，与患者OS呈正相关。经ROC曲线验证分析，发现基于miR-574-5p和miR-497-5p表达计算得到的风险分数是非常有效的预后预测因子。结论：miR-574-5p和miR-497-5p基因参与了宫颈癌的发生发展过程，miR-574-5p和miR-497-5p相当于促癌基因和抑癌基因。基于miR-574-5p和miR-497-5p表达计算得到的风险分数能很好地区分高危险性患者，其有助于对疾病的早期诊断、监测及判断预后，有望成为肿瘤早期诊断及靶向治疗的重要指标。

[1] WANG Z,WANG J,FAN J,et al.Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women:large study in Jiexiu,Shanxi Province,China[J].J Cancer,2017,8(6):924-932.
[2] LI K,YIN R,WANG D,et al.Human papillomavirus subtypes distribution among 2309 cervical cancer patients in West China[J].Oncotarget,2017,8(17):28502-28509.
[3] IORIO M V,CROCE C M.MicroRNA dysregulation in cancer:diagnostics,monitoring and therapeutics.A comprehensive review[J].EMBO Mol Med,2017,9(6):852.
[4] KEΒLER J,ROT S,BACHE M,et al.miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome[J].Oncology Letters,2016,12(6):5281-5288.
[5] BAGNOLI M,PIGNATA S,MEZZANZANICA D.A miRNA signature assessing ovarian cancer prognosis[J].Oncoscience,2016,3(11-12):308-310.
[6] LAGOS-QUINTANA M,RAUHUT R,LENDECKEL W,et al.Identification of novel genes coding for small expressed RNAs[J].Science,2001,294(5543):853-858.
[7] GARZON R,MARCUCCI G,CROCE C M.Targeting micrornas in cancer:Rationale,strategies and challenges[J].Nat Rev Drug Discov,2010,9(10):775-789.
[8] 陈军莹,姚德生,贺婵娟,等.宫颈鳞癌MicroRNA差异表达的研究[J].实用医学杂志,2014,30(1):83-87.
[9] 曾勇,李娜,王福花,等.卵巢浆液性囊腺癌化疗耐药和化疗敏感组织中的miRNAs差异表达谱检测及生物信息学分析[J].现代肿瘤医学,2017,25(12):1870-1875.
[10] GAO D,ZHANG Y,ZHU M,et al.Mirna expression profiles of hpvinfected patients with cervical cancer in the uyghur population in China[J].PLoS One,2016,11(10):e0164701.
[11] LOSSOS I S,CZERWINSKI D K,ALIZADEH A A,et al.Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes[J].N Engl J Med,2004,350(18):1828-1837.
[12] 王治伟,熊裕民,赵子龙.miR-574-5p在乳腺癌患者血清中的水平及与临床病理特征的关系[J].检验医学与临床,2016,13(21):3011-3013.
[13] 周秋媛,王红莉,李虹,等.NRP-1和NRP-2在结直肠癌组织中的表达水平及临床意义[J].现代检验医学杂志,2016,31(6):85-87,91.
[14] WANG X M,LU X B,GENG Z S,et al.LncRNA PTCSC3/miR-574-5p governs cell proliferation and migration of papillary thyroid carcinoma via Wnt/beta-catenin signaling[J].J Cell Biochem,2017,DOI:10.1002/jcb.26142
[15] FOSS K M,SIMA C,UGOLINI D,et al.miR-1254 and miR-574-5p:serum-based microRNA biomarkers for early-stage non-small cell lung cancer[J].J Thorac Oncol,2011,6(3):482-488.
[16] ZHANG W,THEVAPRIYA S,KIM P J,et al.Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex[J].Nat Commun,2014,5:3330.
[17] 任菲,陈军莹,杜萍,等.宫颈癌组织miR-574-5p的表达及其下调后对宫颈癌SiHa细胞的影响[J].基础医学与临床,2015,35(4):458-462.
[18] 张君,高兰阳,詹平,等.miR-497-5p对人宫颈癌细胞增殖的抑制作用及机制[J].山东医药,2017,57(5):15-18.
[19] ZHANG N,SHEN Q,ZHANG P.miR-497 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1[J].Onco Targets Ther,2016,9:6597-6604.
[20] LIU A,HUANG C,CAI X,et al.Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis[J].Oncotarget,2016,7(18):25801-25814.
[21] GU A,LU J,WANG W,et al.Role of miR-497 in VEGF-A-mediated cancer cell growth and invasion in non-small cell lung cancer[J].Int J Biochem Cell Biol,2016,70:118-125.
[22] ZHANG Y,ZHANG D,WANG F,et al.Serum miRNAs panel(miR-16-2*,miR-195,miR-2861,miR-497) as novel non-invasive biomarkers for detection of cervical cancer[J].Sci Rep,2015,5:17942.
[23] SHEN L,LI J,XU L,et al.miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w[J].Exp Ther Med,2012,3(3):475-480.
[24] 刘海峰,刘红伟,马宝新.血清中异常表达的微小RNA-324-5p在动脉粥样硬化诊断和预后评估中的价值分析[J].东南大学学报(医学版),2020,39(1):48-52.