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- 2016
胃癌患者血清miR-101与miR-25的动态变化及其诊断价值
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Abstract:
摘要 目的：探讨miR-101与miR-25在胃癌术前术后血清中的表达及其与病理因素间的关系,探讨其是否能作为胃癌早期诊断的新型生物标志物.方法：应用实时荧光定量(PCR)检测58例胃癌(其中31例配对胃癌术前术后),30例胃癌癌前病变,30例正常对照血清miR-101与miR-25的相对表达量,比较miR-101与miR-25在胃癌术前术后表达差异,及其与病理参数的关系,绘制研究对象工作特征曲线(ROC),评估血清miR-101与miR-25对胃癌的临床诊断价值.结果：胃癌血清miR-101表达水平显著性低于正常对照组(P<0.01)及胃癌癌前病变组(P<0.01),而胃癌血清miR-25(P<0.01)表达水平显著升高.胃癌术后血清miR-101表达水平明显高于术前(P=0.007),而血清miR-25在胃癌术后显著性降低(P=0.011).ROC曲线分析显示血清miR-101与miR-25对胃癌诊断价值较高[miR-101:ROC曲线下面积(Area Under roc Curve, AUC)=0.857,敏感度=0.710,特异度=0.881;miR-25:AUC=0.821,敏感度=0.702,特异度=0.800],而血清miR-101与miR-25联合诊断胃癌的AUC为0.905,其敏感性和特异性分别为75.9%和86.7%.进一步分析发现胃癌血清miR-101低表达与幽门螺旋杆菌(helicobacter pylori,Hp)感染有关,miR-101表达水平在感染HP的胃癌血清中显著低于未感染HP的胃癌血清(P=0.012);胃癌血清miR-101低表达与胃癌淋巴结转移(P=0.033)和临床分期(P=0.015)显著相关;胃癌血清miR-25在高临床分期(P=0.018)和淋巴结转移(P<0.001)表达水平升高.结论：血清miR-101与miR-25可能作为胃癌术前术后动态监测和胃癌诊断的新型潜在标志物.
| [1] | NILSSON P J, VAN E B, HOSPERS G A, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer——the RAPIDO trial[J]. BMC Cancer, 2013, 13(11):279. |
| [2] | CARPELAN H M, LOUHIMO J, STENMAN U H, et al. CEA, CA 19-9 and CA 72-4 improve the diagnostic accuracy in gastrointestinal cancers[J]. Anticancer Res, 2002,22(4):2311-2316. |
| [3] | GILAD S, MEIRI E, YOGEV Y, et al. Serum microRNAs are promising novel biomarkers[J].PLoS One,2008,3(5):e3148. |
| [4] | YAN Y R, ZHOU X L, XIA M H, et al. Correlation of microRNA-21 expression with TGF-β1 in breast cancer[J].暨南大学学报(自然科学与医学版),2011,32(2):176-180. |
| [5] | ZHAO H, WANG Y, YANG L, et al. MiR-25 promotes gastric cancer cells growth and motility by targeting RECK[J]. Mol Cell, 2014,20(7):e213. |
| [6] | LI B S, ZUO Q F, ZHAO Y L, et al. MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival[J]. Oncogene,2014, 34(20):2556-2565. |
| [7] | WANG H J, RUAN H J, HE X J, et al. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion[J]. Eur J Cancer, 2010, 46(12): 2295-2303. |
| [8] | JOANA C, NICOLE C V, PATRICIA M, et al. Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer[J]. J Pathol, 2012, 22(8): 31-44. |
| [9] | TSUJIURE M, ICHIKAWA D, KOMATSU S, et al. Circulating microRNAs in plasma of patients with gastric cancers[J]. Cancer, 2010,102(17):1174-1179. |
| [10] | GUO F, COGDELL D, HU L, et al. MiR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and ZEB2 in ovarian carcinoma[J]. Oncol Rep, 2014,31(5):2021-2028. |
| [11] | THIERY J P, ACLOQUE H, HUANG R Y, et al. Epithelial-mesenchymal transitions in development and disease[J]. Cell, 2009,139(8):71-90. |
| [12] | MOTOYAMA K, INOUE H, NAKAMURA Y, et al.Clinical significance of high mobilitygroup A2 in human gastric cancer and its relationship to let-7 microRNA family[J]. Clin Cancer Res, 2008, 14(8):2334-2340. |
| [13] | HE X P, SHAO Y, LI X L, et al. Downregulation of miR-101 in gastric cancer correlates with cyclooxygenase-2 overexpression and tumor growth[J]. FEBS Journal,2012,27(9): 4201-4212. |
| [14] | ISMAEL R, OSCAUR T, LEAL P, et al. miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in gastric cancer through regulationof the PI3K/AKT/mTOR pathway[J]. Cell Oncol, 2015,9(12):235-247. |
| [15] | LI B S, ZUO Q F, ZHAO Y L, et al.microRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival[J]. Oncogene, 2015, 34(20):2556-2565. |
| [16] | ZHANG M, WANG X, LI W, et al. miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells[J]. Biochem Biophys Res Commun, 2015, 460(21): 806-812. |
| [17] | ZHOU X, XIA Y, LI L, et al. MiR-101 inhibits cell growth and tumorigenesis of Helicobacter pylori related gastric cancer by repression of SOCS2[J].Cancer Biology & Therapy, 2015, 16(1): 160-169. |
| [18] | FERLAYJ, SOERJOMATARAM I, DIKSHIT R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer,2015, 136(3): E359-E386. |
| [19] | ZHANG J, SONG Y, ZHANG C, et al. Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer[J]. Theranostics, 2015, 5(7):733-745. |
| [20] | DHAYAT S A, HUSING A, SENNINGER N, et al.Circulating microRNA-200 Family as Diagnostic Marker in Hepatocellular Carcinoma[J]. 2015,10(10):e0140066. |
| [21] | KoONISHI H, ICHIKAWA D, KOMATSU S, et al. Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma[J]. Br J Cancer, 2012,106(15):740-777. |
| [22] | SONG M Y, PAN K F, SU H J, et al. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer[J]. PLoS ONE, 2012,7(2):e33608. |
| [23] | ZHOU X, XIA Y, SU J, et al. Down-regulation of miR-141 induced by helicobacter pylori promotes the invasion of gastric cancer by targeting STAT4[J]. Cell Physiol Biochem, 2014, 33(4):1003-1012. |
