卵巢癌患者血清miR-210、miR-126与临床病理特征及预后关系探讨
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摘要
目的:研究卵巢癌患者血清微小RNA-210(miR-210)和微小RNA-126(miR-126)表达水平及其与患者临床病理特征及预后的关系。方法:选取102例本院确诊的卵巢癌患者作为观察组,另选取同期本院健康体检的女性志愿者102例为对照组。采用qRT-PCR法检测两组血清miR-210、miR-126相对表达量,根据检测中位值将miR-210、miR-126分为高表达组与低表达组,观察其与患者临床病理特征的关系,受试者工作特征曲线(ROC)法分析miR-210、miR-126表达对卵巢癌的预测价值,Kaplan-Meier分析卵巢癌患者生存,logistic多元回归分析影响卵巢癌发生的危险因素。结果:与对照组相比,观察组血清miR-210表达水平升高,miR-126表达水平降低(P<0.05);miR-210、miR-126均与患者淋巴结转移、FIGO分期、分化程度及糖类抗原125水平相关,且miR-210与组织类型相关(P<0.05);miR-210、miR-126的曲线下面积分别为0.789、0.836,敏感度分别为96.6%、67.8%,特异度分别为51.2%、95.4%;miR-210低表达组无生存进展期(PFS)、总体生存时间(OS)均高于高表达组,miR-126高表达组PFS、OS均高于低表达组(P<0.05);miR-210、miR-126均为影响卵巢癌发生的独立危险因素。结论:卵巢癌患者的血清miR-210上调表达, miR-126下调表达,均与卵巢癌发生发展有关,均可能作为临床诊断、监测病情及评估预后的重要指标。
Objective: To study the expression levels of serum micro RNA-210(miR-210) and micro RNA-126(miR-126) of patients with ovarian cancer, and to explore the relationships between the levels of miR-210 and miR-126 and the clinicopathological features and prognosis of the patients. Methods: 102 patients with ovarian cancer were selected in study group, and another 102 healthy female volunteers were selected in control group. The expression levels of serum miR-210 and miR-126 of women in the two groups were detected by qRT-PCR, and women in study group were divided into high expression group and low expression group according to the median value of the levels of serum miR-210 and miR-126. Receiver operating characteristic curve(ROC) was used to analyze the predictive values of miR-210 and miR-126 expressions, Kaplan-Meier was used to analyze the survival of patients with ovarian cancer, and Logistic multiple regression analysis was used to analyze the risk factors of ovarian cancer. Results: Compared with the control group, the expression level of serum miR-210 of patients in study group increased(P<0.05), but the expression level of miR-126 was decreased significantly(P<0.05). MiR-210 and miR-126 levels were significantly correlated with lymph node metastasis, FIGO stage, degree of differentiation, and the serum carbohydrate antigen 125(CA125) level of patients(P<0.05), and miR-210 level was significantly correlated with histological type(P<0.05). ROC analysis showed that the area under curve(AUC) of miR-210 level and miR-126 level were 0.789 and 0.836, respectively, their sensitivity were 96.61% and 67.80%, respectively, and their specificity were 51.16% and 95.35%, respectively.
Objective: To study the expression levels of serum micro RNA-210(miR-210) and micro RNA-126(miR-126) of patients with ovarian cancer, and to explore the relationships between the levels of miR-210 and miR-126 and the clinicopathological features and prognosis of the patients. Methods: 102 patients with ovarian cancer were selected in study group, and another 102 healthy female volunteers were selected in control group. The expression levels of serum miR-210 and miR-126 of women in the two groups were detected by qRT-PCR, and women in study group were divided into high expression group and low expression group according to the median value of the levels of serum miR-210 and miR-126. Receiver operating characteristic curve(ROC) was used to analyze the predictive values of miR-210 and miR-126 expressions, Kaplan-Meier was used to analyze the survival of patients with ovarian cancer, and Logistic multiple regression analysis was used to analyze the risk factors of ovarian cancer. Results: Compared with the control group, the expression level of serum miR-210 of patients in study group increased(P<0.05), but the expression level of miR-126 was decreased significantly(P<0.05). MiR-210 and miR-126 levels were significantly correlated with lymph node metastasis, FIGO stage, degree of differentiation, and the serum carbohydrate antigen 125(CA125) level of patients(P<0.05), and miR-210 level was significantly correlated with histological type(P<0.05). ROC analysis showed that the area under curve(AUC) of miR-210 level and miR-126 level were 0.789 and 0.836, respectively, their sensitivity were 96.61% and 67.80%, respectively, and their specificity were 51.16% and 95.35%, respectively.
引文
[1] 刘妍, 刘颖, 俊梅, 等. 卵巢癌患者血清CD133和miR-145的表达与临床病理特征及预后的关系[J]. 中国妇幼保健, 2017, 32(14): 3155-3158.
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[12] Zahng C, Tian W, Meng L, et al. PRL-3 promotes gastric cancer migration and invasion through a NF-κB-HIF-1α-miR-210 axis[J]. J Mol Med, 2016, 94(4): 401-415.
[13] Li Y, Dai Y, Zhang X, et al. Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy[J]. Nanotechnology, 2017, 28(28): 285101.
[14] 蓝永洪, 牛海艳, 王晗, 等. miR-210对乳腺癌细胞生物学行为的影响[J]. 安徽医科大学学报, 2017, 52(1): 83-85.
[15] Hu MH, Ma CY, Wang XM, et al. MicroRNA-126 inhibits tumor proliferation and angiogenesis of hepatocellular carcinoma by down-regulating EGFL7 expression[J]. Oncotarget, 2016, 7(41): 66922-66934.
[16] Cuiffo BG, Campagne A, Bell GW, et al. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis[J]. Cell Stem Cell, 2014, 15(6): 762-774.
[17] Wang JN, Yan YY, Guo ZY, et al. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention[J]. Chin Med J, 2016, 129(23): 2786-2791.
[18] Feng R, Beeharry MK, Lu S, et al. Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer[J]. Cancer Biomark, 2018, 22(1): 119-126.
[2] Dong X, Men X, Zhang W, et al. Advances in tumor markers of ovarian cancer for early diagnosis[J]. Indian J Cancer, 2014, 51(3): s72-76.
[3] Zhang Y, Yang P, Wang XF. Microenvironmental regulation of cancer metastasis by miRNAs[J]. Trends Cell Biol, 2014, 24(3): 153-160.
[4] Block I, Burton M, Serensen KP, et al. Association of miR-548c-5p, miR-7-5p, miR-210-3p, miR-128-3p with recurrence in systemically untreated breast cancer[J]. Oncotarget, 2018, 9(10): 9030-9042.
[5] Bladassari F, Zerbinati C, Galasso M, et al. Screen for MicroRNA and Drug Interactions in Breast Cancer Cell Lines Points to miR-126 as a Modulator of CDK4/6 and PIK3CA Inhibitors[J]. Front Genet, 2018, 9: 174.
[6] 沈铿, 彭澎, 吴鸣. 国际妇产科联盟妇科肿瘤2009年分期的解读[J]. 中华妇产科杂志, 2010, 45(10): 721-724.
[7] 赵丽红, 王娟, 杨晓葵. 卵巢组织中M1/M2巨噬细胞特征分子标志基因表达与组织分化程度的相关关系[J]. 临床和实验医学杂志, 2014, 13(1): 10-13.
[8] 姜丽娜, 张海静, 张海鹰. HE4、CA125及CA72-4在子宫内膜异位症及卵巢癌中的诊断差异研究[J]. 中国实验诊断学, 2014, 18(3): 394-396.
[9] 刘春静, 陈隽, 董冰, 等. 不同分型卵巢癌患者组织中瘦素mRNA表达的相关研究[J]. 中国免疫学杂志, 2017, 33(7): 1084-1086.
[10] Wu HH, Lin WC, Tsai KW. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers[J]. Expert Rev Mol Med, 2014, 16: e1.
[11] Chen Y, Wang X, Zhu X, et al. Detection Performance of Circulating MicroRNA-210 for Renal Cell Carcinoma: a Meta-Analysis[J]. Clin Lab, 2018, 64(4): 569-576.
[12] Zahng C, Tian W, Meng L, et al. PRL-3 promotes gastric cancer migration and invasion through a NF-κB-HIF-1α-miR-210 axis[J]. J Mol Med, 2016, 94(4): 401-415.
[13] Li Y, Dai Y, Zhang X, et al. Three-layered polyplex as a microRNA targeted delivery system for breast cancer gene therapy[J]. Nanotechnology, 2017, 28(28): 285101.
[14] 蓝永洪, 牛海艳, 王晗, 等. miR-210对乳腺癌细胞生物学行为的影响[J]. 安徽医科大学学报, 2017, 52(1): 83-85.
[15] Hu MH, Ma CY, Wang XM, et al. MicroRNA-126 inhibits tumor proliferation and angiogenesis of hepatocellular carcinoma by down-regulating EGFL7 expression[J]. Oncotarget, 2016, 7(41): 66922-66934.
[16] Cuiffo BG, Campagne A, Bell GW, et al. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis[J]. Cell Stem Cell, 2014, 15(6): 762-774.
[17] Wang JN, Yan YY, Guo ZY, et al. Negative Association of Circulating MicroRNA-126 with High-sensitive C-reactive Protein and Vascular Cell Adhesion Molecule-1 in Patients with Coronary Artery Disease Following Percutaneous Coronary Intervention[J]. Chin Med J, 2016, 129(23): 2786-2791.
[18] Feng R, Beeharry MK, Lu S, et al. Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer[J]. Cancer Biomark, 2018, 22(1): 119-126.