KLF4与S100A14在子宫内膜异位症相关性卵巢癌中的表达及临床意义
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摘要
目的:探求子宫内膜异位症相关性卵巢癌中Krüppel样因子4(KLF4)与钙离子结合蛋白14(S100A14)的表达情况及临床意义。方法:免疫组化判定KLF4及S100A14分别在36例正常/良性卵巢组织(对照组)、30例卵巢子宫内膜异位症组织(ovarian endometriosis,OE)和49例子宫内膜异位症相关性卵巢癌组织(endometriosis associated ovarian carcinoma,EAOC)中的表达情况,并分析二者与EAOC患者相关临床参数的关系。结果:KLF4在对照组、OE组以及EAOC组中的阳性表达率分别为72.2%(26/36)、63.3%(19/30)、32.7%(16/49),差异有统计学意义(P<0.01)。S100A14在三组中表达的阳性率分别为61.1%(22/36)、63.3%(19/30)、87.8%(43/49),差异有统计学意义(P<0.05)。在EAOC中,KLF4表达与淋巴结转移有显著相关性(P<0.05)。KLF4与S100A14呈负相关(r=-0.138)。结论:KLF4低表达和S100A14高表达可能参与了卵巢子宫内膜异位症恶变,同时KLF4可能促进了EAOC的转移。
Objective:To investigate the expression and clinical significance of Krüppel-like factor 4(KLF4) and calcium ion-binding protein 14(S100 A14) in endometriosis associated ovarian carcinoma.Methods:To detect the expression of KLF4,S100 A14 in 36 cases of normal/benign ovarian tissues(control group),30 ovarian endometriosis(OE) cases and 49 cases of endometriosis associated ovarian carcinoma(EAOC),analyze the relationship between them and clinical parameters in EAOC by immunohistochemistry.Results:The positive rates of KLF4 in the control group,OE and EAOC were 72.2%(26/36),63.3%(19/30) and 32.7%(16/49),respectively.The difference was statistically significant(P<0.01).The positive rates of S100 A14 in the three groups were 61.1%(22/36),63.3%(19/30),and 87.8%(43/49),respectively(P<0.05).In EAOC,KLF4 expression was significantly correlated with lymph node metastasis(P<0.05).KLF4 was negatively correlated with S100 A14(r=-0.138).Conclusion:Low expression of KLF4 and high expression of S100 A14 may be involved in the development of malignant transformation of ovarian endometriosis,and KLF4 may promote the metastasis of EAOC.
Objective:To investigate the expression and clinical significance of Krüppel-like factor 4(KLF4) and calcium ion-binding protein 14(S100 A14) in endometriosis associated ovarian carcinoma.Methods:To detect the expression of KLF4,S100 A14 in 36 cases of normal/benign ovarian tissues(control group),30 ovarian endometriosis(OE) cases and 49 cases of endometriosis associated ovarian carcinoma(EAOC),analyze the relationship between them and clinical parameters in EAOC by immunohistochemistry.Results:The positive rates of KLF4 in the control group,OE and EAOC were 72.2%(26/36),63.3%(19/30) and 32.7%(16/49),respectively.The difference was statistically significant(P<0.01).The positive rates of S100 A14 in the three groups were 61.1%(22/36),63.3%(19/30),and 87.8%(43/49),respectively(P<0.05).In EAOC,KLF4 expression was significantly correlated with lymph node metastasis(P<0.05).KLF4 was negatively correlated with S100 A14(r=-0.138).Conclusion:Low expression of KLF4 and high expression of S100 A14 may be involved in the development of malignant transformation of ovarian endometriosis,and KLF4 may promote the metastasis of EAOC.
引文
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[13] Li S.The regulation and function of KLF4 in tumorigenesis and development[D].Peking Union Medical College Hospital,2014.[李生.KLF4在肿瘤发生发展中的调控机制及功能研究[D].北京协和医学院,2014.]
[14] Zhao H,Guo E,Hu T,et al.KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer[J].Oncotarget,2016,7(28):43924-43938.
[15] Scott RB.Malignant changes in endometriosis[J].Obstet Gynecol,1953,2(3):283-289.
[16] Wang S,Lang JH.Current status and prospect of the study on ovarian cancer associated with endometriosis[J].Chinese Journal of Practical Gynecology and Obstetrics,2017,33(04):360-364.[王姝,郎景和.子宫内膜异位症相关性卵巢癌的研究现状及展望[J].中国实用妇科与产科杂志,2017,33(04):360-364.]
[2] Shih IeM,Kurman RJ.Ovarian tumorigenesis:A proposed model based on morphological and molecular genetic analysis[J].Am J Pathol,2004,164(5):1511-1518.
[3] Pearce CL,Templeman C,Rossing MA,et al.Association between endometriosis and risk of histological subtypes of ovarian cancer:A pooled analysis of case-control studies[J].Lancet Oncol,2012,13(4):385-394.
[4] Nezhat FR,Apostol R,Nezhat C,et al.New insights in the pathophysiology of ovarian cancer and implications for screening and prevention[J].Am J Obstet Gynecol,2015,213(3):262-267.
[5] Amr M,Ghaleb,Vincent W Yang.Krüppel-like factor 4 (KLF4):What we currently know[J].Gene,2017,611:27-37.
[6] Ghaleb AM,Elkarim EA,Bialkowska AB,et al.KLF4 suppresses tumor formation in genetic and pharmacological mouse models of colonic tumorigenesis[J].Mol Cancer Res,2016,14(4):385-396.
[7] Ding X,Zhong T,Jiang L,et al.miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells via ERK signaling pathway by inhibiting KLF4[J].Mol Med Rep,2018,17(5):7005-7016.
[8] Jia ZM,Ai X,Teng JF,et al.p21 and CK2 interaction-mediated HDAC2 phosphorylation modulates KLF4 acetylation to regulate bladder cancer cell proliferation[J].Tumour Biol,2016,37(6):8293-8304.
[9] Li W,Liu M,Su Y,et al.The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells[J].Oncotarget,2015,6(42):44480-44494.
[10] Pietas A,Schlüns K,Marenholz I,et al.Molecular cloning and characterization of the human S100A14 gene encoding a novel member of the S100 family[J].Genomics,2002,79(4):513-522.
[11] Katono K,Sato Y,Kobayashi M,et al.Clinicopathological significance of S100A14 expression in lung adenocarcinoma[J].Oncol Res Treat,2017,40(10):594-602.
[12] He H,Li S,Chen H,et al.12-O-tetradecanoylphorbol-13-acetate promotes breast cancer cell motility by increasing S100A14 level in a Kruppel-like transcription factor 4 (KLF4)-dependent manner[J].J Biol Chem,2014,289(13):9089-9099.
[13] Li S.The regulation and function of KLF4 in tumorigenesis and development[D].Peking Union Medical College Hospital,2014.[李生.KLF4在肿瘤发生发展中的调控机制及功能研究[D].北京协和医学院,2014.]
[14] Zhao H,Guo E,Hu T,et al.KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer[J].Oncotarget,2016,7(28):43924-43938.
[15] Scott RB.Malignant changes in endometriosis[J].Obstet Gynecol,1953,2(3):283-289.
[16] Wang S,Lang JH.Current status and prospect of the study on ovarian cancer associated with endometriosis[J].Chinese Journal of Practical Gynecology and Obstetrics,2017,33(04):360-364.[王姝,郎景和.子宫内膜异位症相关性卵巢癌的研究现状及展望[J].中国实用妇科与产科杂志,2017,33(04):360-364.]