血清miRNA-93、miRNA-223联合miRNA-324-3p可作为诊断PCOS的生物标记物
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摘要
本研究拟基于最近的miRNA报道,结合前期关于肌肉生长抑素(myostatin, MSTN)的相关研究,探究多囊卵巢综合症(ploycystic ovary syndrome, PCOS)患者血清miRNA和生长抑素的表达及其相关临床病理特征。本研究选取160例在湘南学院附属医院妇科就诊的女性为研究对象,通过PCR、ELISA等方法比较PCOS患者血清miRNA和生长抑素的表达情况,并且分析其相关临床病理特征。结果显示,通过PCR的方法发现mi RNA-93、mi RNA-223在PCOS患者的血清中显著升高,而mi RNA-4522、mi RNA-6767-5p和mi RNA-324-3p则表达下降。本研究建立了3个miRNA的预测模型,并证实预测模型在筛选组和验证组中有很好的敏感性和特异性,可以有效区分PCOS患者和正常人群,但研究结果也发现,miRNA模型结合MSTN没有更好的诊断价值。
Based on the recent reports of miRNAs, combined with previous researches related to muscle somatostatin(MSTN), this study explored the expression of serum miRNAs and MSTN in patients with ploycystic ovary syndrome(PCOS) and its related clinical pathological features. This research chose 160 cases of females visiting Gynecology Department of Xiangnan University Affiliated Hospital as subjects, the expression of serum miRNA and MSTN in patients with PCOS patients were compared by PCR and ELISA, and the related clinical pathologic features were analyzed as well. The results showed that the expression of miRNA-93 and miRNA-223 was significantly increased in serum of patients with PCOS, while the expression of miRNA-4522, miRNA-6767-5 p, and miRNA-6767-3 p was decreased. The study established a "3-miRNAs"model, and confirmed the prediction model had well sensitivity and specificity in screening group and validation group, which could effectively distinguish PCOS patients and normal people. The research results found that miRNA model combined with MSTN had no better diagnostic value.
Based on the recent reports of miRNAs, combined with previous researches related to muscle somatostatin(MSTN), this study explored the expression of serum miRNAs and MSTN in patients with ploycystic ovary syndrome(PCOS) and its related clinical pathological features. This research chose 160 cases of females visiting Gynecology Department of Xiangnan University Affiliated Hospital as subjects, the expression of serum miRNA and MSTN in patients with PCOS patients were compared by PCR and ELISA, and the related clinical pathologic features were analyzed as well. The results showed that the expression of miRNA-93 and miRNA-223 was significantly increased in serum of patients with PCOS, while the expression of miRNA-4522, miRNA-6767-5 p, and miRNA-6767-3 p was decreased. The study established a "3-miRNAs"model, and confirmed the prediction model had well sensitivity and specificity in screening group and validation group, which could effectively distinguish PCOS patients and normal people. The research results found that miRNA model combined with MSTN had no better diagnostic value.
引文
Acunz o M.,Ro mano G.,Wernicke D.,and Croce C.M.,2015,MicroRNA and cancer--a brief overview,Adv.Biol.Regul.,(57):1-9
Azziz R.,Carmina E.,Dewailly D.,Diamanti-Kandarakis E.,Escobar-Morreale H.F.,Futterweit W.,Janssen O.E.,Legro R.S.,Norman R.J.,Taylor A.E.,and Witchel S.F.,2009,The androgen excess and PCOS society criteria for the polycystic ovary syndrome:the complete task force report,Fertil and Steril,91(2):456-488
Flynt A.S.,and Lai E.C.,2008,Biological principles of microR-NA-mediated regulation:shared themes amid diversity,Nat.Re.Genet.,9(11):831-842
Hao W.,Guo Y.,Hao G.M.,and Wang W.,2016,Research progress on mi RNA-related mechanism of polycystic ovary syndrome,Shengzhi Yixue Zazhi(Journal of Reproductive Medicine),25(12):1126-1129(郝薇,郭影,郝桂敏,王玮,2016,mi RNA与多囊卵巢综合征发病机制相关性的研究进展,生殖医学杂志,25(12):1126-1129)
Liu M.,and Wang L.,2014,The advance on the relationship between genetic polymorphism and the pathogenesis of PCOS,Zhongguo Linchuang Xinyixue(Chinese Journal of New Clinical Medicine),(3):272-276(刘敏,王琳,2014,基因多态性与PCOS发病机制相关性研究近况,中国临床新医学,(3):272-276)
Li G.,Liu Y.,Su Z.,Liu C.,Ren S.,Deng T.,Huang D.,Tian Y.,and Qiu Y.,2013,MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B in vitro,Eur.J.Cancer.,49(11):2596-2607
Liu S.,Zhang X.,Shi C.,Lin J.,Chen G.,Wu B.,Wu L.,Shi H.,Yuan Y.,Zhou W.,Sun Z.,Dong X.,and Wang J.,2015,Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome,J.Transl.Med.,13:238
Long W.,Zhao C.,and Ji C.,Ding H.,Guo X.,Shen R.,and Liu J.,2014,Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers,Cell Physiol Biochem,33(5):1304-1315
Manneras-Holm L.,Benrick A.,and Stener-Victorin E.,2014,Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age,body weight,and body mass index,Adipocyte,3(3):190-196
Stepto N.K.,Cassar S.,Joham A.E.,Hutchison S.K.,Harrison C.L.,Goldstein R.F.,and Teede H.J.,2013,Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp,Hum.Reprod.,28(3):777-784
Sorensen A.E.,Wissing M.L.,Salo S.,Englund A.L.,and Dalgaard L.T.,2014,MicroRNAs related to polycystic ovary syndrome(PCOS),Genes(Basel),5(3):684-708
Sorensen A.E.,Udesen P.B.,Wissing M.L.,Englund A.L.,and Dalgaard L.T.,2016,MicroRNAs related to and rogen metabolism and polycystic ovary syndrome,Chem.Biol.Interact.,259(Pt A):8-16
S athyapalan T.,David R.,Gooderham N.J.,and Atkin S.L.,2015,Increased expression of circulating mi RNA-93 in women with polycystic ovary syndrome may represent a novel,non-invasive biomarker for diagnosis,Sci.Rep.,5:16890
Song D.K.,Sung Y.A.,and Lee H.,2016,The role of serum microRNA-6767-5p as a biomarker for the diagnosis of polycystic ovary syndrome,PLoS One,11(9):e163756
Sempere L.F.,2014,Tissue slide-based microRNA characterization of tumors:how detailed could diagnosis become for cancer medicine,Expert.Rev.Mol.Diagn.,14(7):853-869
Teede H.J.,Joham A.E.,Paul E.,Moran L.J.,Loxton D.,Jolley D.,and Lombard C.,2013,Longitudinal weight gain in women identified with polycystic ovary syndrome:results of an ob servational study in young women,Obesity(Silver Spring),21(8):1526-1532
Wu H.L.,Heneidi S.,Chuang T.Y.,Michael P.D.,Lawrence C.L.,Ricardo A.,and ChenY.H.,2014,The expression of the mi R-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome,J.Clin.Endocrinol.Metab.,99(12):2754-2761
Xu D.,Chen X.,He Q.,and Lou C.,2016,MicroRNA-9 suppresses the growth,migration,and invasion of malignant melanoma cells via targeting NRP1,Oncotargets and Therapy,(9):7047-7057
Xiao Y.,Su C.,and Deng T.,2016,mi R-223 decreases cell proliferation and enhances cell apoptosis in acute myeloid leukemia via targeting FBXW7,Oncol.Lett.,12(5):3531-3536
Yildiz B.O.,Bozdag G.,Yapici Z.,Esinler I.,and Yarali H.,2012,Prevalence,phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria,Hum.Reprod.,27(10):3067-3073
Azziz R.,Carmina E.,Dewailly D.,Diamanti-Kandarakis E.,Escobar-Morreale H.F.,Futterweit W.,Janssen O.E.,Legro R.S.,Norman R.J.,Taylor A.E.,and Witchel S.F.,2009,The androgen excess and PCOS society criteria for the polycystic ovary syndrome:the complete task force report,Fertil and Steril,91(2):456-488
Flynt A.S.,and Lai E.C.,2008,Biological principles of microR-NA-mediated regulation:shared themes amid diversity,Nat.Re.Genet.,9(11):831-842
Hao W.,Guo Y.,Hao G.M.,and Wang W.,2016,Research progress on mi RNA-related mechanism of polycystic ovary syndrome,Shengzhi Yixue Zazhi(Journal of Reproductive Medicine),25(12):1126-1129(郝薇,郭影,郝桂敏,王玮,2016,mi RNA与多囊卵巢综合征发病机制相关性的研究进展,生殖医学杂志,25(12):1126-1129)
Liu M.,and Wang L.,2014,The advance on the relationship between genetic polymorphism and the pathogenesis of PCOS,Zhongguo Linchuang Xinyixue(Chinese Journal of New Clinical Medicine),(3):272-276(刘敏,王琳,2014,基因多态性与PCOS发病机制相关性研究近况,中国临床新医学,(3):272-276)
Li G.,Liu Y.,Su Z.,Liu C.,Ren S.,Deng T.,Huang D.,Tian Y.,and Qiu Y.,2013,MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B in vitro,Eur.J.Cancer.,49(11):2596-2607
Liu S.,Zhang X.,Shi C.,Lin J.,Chen G.,Wu B.,Wu L.,Shi H.,Yuan Y.,Zhou W.,Sun Z.,Dong X.,and Wang J.,2015,Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome,J.Transl.Med.,13:238
Long W.,Zhao C.,and Ji C.,Ding H.,Guo X.,Shen R.,and Liu J.,2014,Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers,Cell Physiol Biochem,33(5):1304-1315
Manneras-Holm L.,Benrick A.,and Stener-Victorin E.,2014,Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age,body weight,and body mass index,Adipocyte,3(3):190-196
Stepto N.K.,Cassar S.,Joham A.E.,Hutchison S.K.,Harrison C.L.,Goldstein R.F.,and Teede H.J.,2013,Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp,Hum.Reprod.,28(3):777-784
Sorensen A.E.,Wissing M.L.,Salo S.,Englund A.L.,and Dalgaard L.T.,2014,MicroRNAs related to polycystic ovary syndrome(PCOS),Genes(Basel),5(3):684-708
Sorensen A.E.,Udesen P.B.,Wissing M.L.,Englund A.L.,and Dalgaard L.T.,2016,MicroRNAs related to and rogen metabolism and polycystic ovary syndrome,Chem.Biol.Interact.,259(Pt A):8-16
S athyapalan T.,David R.,Gooderham N.J.,and Atkin S.L.,2015,Increased expression of circulating mi RNA-93 in women with polycystic ovary syndrome may represent a novel,non-invasive biomarker for diagnosis,Sci.Rep.,5:16890
Song D.K.,Sung Y.A.,and Lee H.,2016,The role of serum microRNA-6767-5p as a biomarker for the diagnosis of polycystic ovary syndrome,PLoS One,11(9):e163756
Sempere L.F.,2014,Tissue slide-based microRNA characterization of tumors:how detailed could diagnosis become for cancer medicine,Expert.Rev.Mol.Diagn.,14(7):853-869
Teede H.J.,Joham A.E.,Paul E.,Moran L.J.,Loxton D.,Jolley D.,and Lombard C.,2013,Longitudinal weight gain in women identified with polycystic ovary syndrome:results of an ob servational study in young women,Obesity(Silver Spring),21(8):1526-1532
Wu H.L.,Heneidi S.,Chuang T.Y.,Michael P.D.,Lawrence C.L.,Ricardo A.,and ChenY.H.,2014,The expression of the mi R-25/93/106b family of micro-RNAs in the adipose tissue of women with polycystic ovary syndrome,J.Clin.Endocrinol.Metab.,99(12):2754-2761
Xu D.,Chen X.,He Q.,and Lou C.,2016,MicroRNA-9 suppresses the growth,migration,and invasion of malignant melanoma cells via targeting NRP1,Oncotargets and Therapy,(9):7047-7057
Xiao Y.,Su C.,and Deng T.,2016,mi R-223 decreases cell proliferation and enhances cell apoptosis in acute myeloid leukemia via targeting FBXW7,Oncol.Lett.,12(5):3531-3536
Yildiz B.O.,Bozdag G.,Yapici Z.,Esinler I.,and Yarali H.,2012,Prevalence,phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria,Hum.Reprod.,27(10):3067-3073
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