Expression and clinical significance of DLK1 and MMP-9 in cholangiocarcinoma
-
摘要:
目的通过观察胆管癌组织中穿膜蛋白1(DLK1)与基质金属蛋白酶9(MMP-9)的表达,分析两者的临床意义及相关性。方法收集2001-2010年96例胆管癌患者癌组织,20例正常人胆管组织作为对照,采用SP免疫组织化学法检测组织中DLK1与MMP-9的表达。组间比较采用卡方检验,相关性检验采用Spearman相关分析。结果 DLK1与MMP-9在胆管癌中的阳性表达率分别为59.38%和79.17%,2者显著高于在正常胆管组织中的表达(0和15%),差异有统计学意义(χ2=23.35、31.37,P<0.05)。胆管癌中DLK1的表达与肿瘤的分化程度相关(χ2=7.46,P<0.05);MMP-9的表达与肿瘤的分化程度、淋巴结转移相关(χ2=7.28、9.67,P<0.05),与性别、年龄、肿瘤组织大小无关(p>0.05)。两者在胆管癌组织中的表达呈正相关(r=0.41,P<0.05)。结论 DLK1与MMP-9在胆管癌中高表达,且两者呈正相关,提示可能与胆管癌的发生、发展、侵润、转移有关,其表达的检测为胆管癌的诊断及治疗提供一定的参考依据。
Abstract:Objective To investigate the expression of delta drosophila homolog- like 1 ( DLK1) and matrix metalloproteinase 9 ( MMP- 9) in cholangiocarcinoma tissue and to analyse their clinical significance and the correlation between DLK1 and MMP- 9. Methods Cholangiocarcinoma tissues were collected from 96 patients who were pathologically diagnosed with cholangiocarcinoma from 2001 to 2010, and normal bile duct tissues were collected from 20 normal persons. The expression of DLK1 and MMP- 9 in cholangiocarcinoma tissues or normal bile duct tissues was measured by immunohistochemical S- P method. Chi- square test was performed using SPSS 17. 0. Correlation analysis was performed by Spearman's correlation test. Results The positive expression rates of DLK1 and MMP- 9 in cholangiocarcinoma tissues were 59. 38% and 79. 17%, respectively, significantly higher than those in normal bile duct tissues ( 0 and 15%) ( χ2= 23. 35, P < 0. 05; χ2= 31. 37, P < 0. 05) . The expression of DLK1 was correlated with the differentiation degree in cholangiocarcinoma ( χ2= 7. 46, P < 0. 05) ; the expression of MMP- 9 was correlated with the differentiation degree and lymph node metastasis in cholangiocarcinoma ( χ2= 7. 28, P < 0. 05; χ2= 9. 67, P < 0. 05) , but was not correlated with sex, age, and tumor size ( P > 0. 05) . There was a positive correlation between the expression of DLK1 and MMP- 9 ( r = 0. 41, P < 0. 05) . Conclusion DLK1 and MMP- 9 are highly expressed in cholangiocarcinoma, and they are positively correlated, suggesting that they are associated with the development, progression, invasion, and metastasis of cholangiocarcinoma. The detection of the two indicators provides a reference for the diagnosis and treatment of cholangiocarcinoma.
-
[1]GENG JH, YUAN JF, WU M, et al.Distribution on epidemiological survey and risk factor for gallbladder cancer[J].J Clin Exp Med, 2012, 11 (16) :1336-1337. (in Chinese) 耿金宏, 袁金凤, 吴鸣, 等.胆囊癌流行分布及高危因素探讨研究[J].临床和实验医学杂志, 2012, 11 (16) :1336-1337. [2]ZHU NL, ASAHINA K, WANG J, et al.Hepatic stellate cell-derived Delta-like Homolog 1 (DLK1) protein in liver regeneration[J].J Biol Chem, 2012, 287 (13) :10355-10367. [3]PAN RL, WANG P, XIANG LX, et al.Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation[J].J Biol Chem, 2011, 286 (14) :12340-12348. [4]HUANG J, ZHANGX, ZHANG M, et al.Up-regulation of DLK1as an imprinted gene could contribute to humanhepatocellular carcinoma[J].Carcinogenesis, 2007, 28 (5) :1094-1103. [5]HUANG CC, CHUANG JH, HUANG LL, et al.The human Delta-like 1 homologue is implicated in the progression of liver fibrosis in biliary atresia[J].J Pathol, 2004, 202 (2) :172-179. [6]LEE SO, JEONG YJ, KIM M, et al.Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition of NFkappa B-dependent MMP-9 expression[J].Biochem Biophys Res Commun, 2008, 366 (4) :1019-1024. [7]ZHAO M, GAO Y, WANG L, et al.Overexpression of integrinlinked kinase promotes lung cancer cell migration and invasion via NF-κB-mediated upregulation of matrix metalloproteinase-9[J].Int J Med Sci, 2013, 10 (8) :995-1002. [8]SHIRABE K, SHIMADA M, KAJIYAMA K, et al.Expression of matrix metalloproteinase-9 in surgically resected intrahepatie cholangiocarcinoma[J].Surgery, 1999, 126 (5) :842-846. [9]DENNING MF, DLUGOSZ AA, CHENG C, et al.Cross-talk between epidermalgrowth factor receptor and protein kinase D during calcium induceddifferentiation of keratinocytes[J].Exp Dermatol, 2000, 9:192-199. [10]ELLENRIEDER V, HENDLER SF, RUHLAND C, et al.TGF-β-induced invasiveness of pancreatic cancer cells is mediated by matrix metalloproteinase-2 and the urokinase plasminogen activator system[J].Int J Cancer, 2001, 93 (2) :204-211. [11]ABOUNADER R, RANGANATHAN S, LAL B, et al.Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/HGF and c-met expression[J].J Natl Cancer Inst, 1999, 91 (18) :1548-1556. [12]SUNDARAM MV.The love hate relationship between Ras and Notch[J].Genes Dev, 2005, 19 (16) :1825-1839. [13]Huang B, Zhao GZ.Expressions of AnnexinⅡand Ki-6 in cholangiocarcinoma and their clinicopathological significance[J].J Clin Hepatol, 2011, 27 (2) :178-180. (in Chinese) 黄波, 赵国忠.AnnexinⅡ和Ki-67在胆管癌中的表达及意义[J].临床肝胆病杂志, 2011, 27 (2) :178-180. [14]KHAN SA, TOMAS HC, TOLEDANO MB, et al.P53 mutations in human cholangiocarcinoma:a review[J].Liver Int, 2005, 25 (4) :704-716.
计量
- 文章访问数: 3169
- HTML全文浏览量: 22
- PDF下载量: 685
- 被引次数: 0