Gremlin-1在原发性肝癌及肝硬化患者中的表达及意义

郭永红; 陈琳; 张颖; 贾晓黎; 翟松; 周云; 何瑜; 纪光晰; 贾战生

doi:10.3969/j.issn.1001-5256.2014.03.013

Gremlin-1在原发性肝癌及肝硬化患者中的表达及意义

DOI: 10.3969/j.issn.1001-5256.2014.03.013

1. 第四军医大学唐都医院全军感染病诊疗中心
2. 西安交通大学医学院第二附属医院感染科
3. 第四军医大学唐都医院质量控制科

基金项目:

国家自然科学基金(81100300)；

详细信息

中图分类号: R735.7;R575.2
计量
- 文章访问数: 2997
- HTML全文浏览量: 12
- PDF下载量: 598
- 被引次数: 0
出版历程
- 出版日期: 2014-03-20

Expression and clinical significance of Gremlin-1 in patients with primary liver cancer and liver cirrhosis

Research funding:

摘要

摘要:
目的检测Gremlin-1在原发性肝癌及肝硬化患者外周血单个核细胞（PBMC）及肝脏组织中的表达。方法收集2012年6-12月在第四军医大学唐都医院就诊的21例原发性肝癌及17例肝硬化患者血样,15名健康志愿者作为对照。采用RT-PCR技术检测PBMC中Gremlin-1的表达;免疫组织化学方法检测10例原发性肝癌肝组织中Gremlin-1的表达。组间比较采用ANOVA方差分析。结果 Gremlin-1在原发性肝癌及肝硬化患者PBMC中表达显著升高,分别为正常对照的3.5及4.4倍,与正常对照相比差异有统计学意义（P=0.003 4,0.002 6）;Gremlin-1在肝癌患者肝组织中高表达,阳性率为72.5%,在正常肝组织中低表达或无表达,阳性率为12.1%,差异有统计学意义（P<0.001）,gremlin-1在高分化及低分化肿瘤表达差异无统计学意义（p>0.05）;免疫组织化学显示Gremlin-1主要表达在肝肿瘤细胞膜及细胞质,部分表达在血管内皮细胞、成纤维细胞等间质细胞。结论Gremlin-1的表达与肝硬化及原发性肝癌密切相关。
- Gremlin-1 /
- 肝肿瘤 /
- 肝硬化
Abstract:
Objective To measure the expression of Gremlin- 1 in the peripheral blood mononuclear cells ( PBMCs) and liver tissues of patients with primary liver cancer and liver cirrhosis. Methods PBMCs were obtained from 21 patients with primary liver cancer and 17 patients with liver cirrhosis during June to December 2012, as well as 15 healthy donors as control. The mRNA expression of Gremlin- 1 in PBMCs was measured by real- time quantitative PCR; the expression of Gremlin- 1 in the liver tissues of 10 patients with primary liver cancer was measured by immunohistochemistry. Comparison between groups was made by analysis of variance. Results Compared with that in control group, the mRNA expression of Gremlin- 1 in PBMCs was up- regulated by 3. 5 and 4. 4 times in patients with primary liver cancer and liver cirrhosis, respectively ( P = 0. 003 4; P = 0. 002 6) . Gremlin- 1 was highly expressed in the liver tissues of patients with primary liver cancer, with a positive rate of 72. 5%, while it was lowly or not expressed in the normal liver tissue, with a positive rate of 12. 1%; there was a significant difference in the positive rate between patients with primary liver cancer and the control group ( P < 0. 001) , but there was no significant difference in the positive rate between poorly differentiated carcinoma and well differentiated carcinoma ( 74. 7% vs 69. 1%, P > 0. 05) . The immunohistochemistry showed that Gremlin- 1 was expressed mainly in the cell membrane and cytoplasm of liver tumor and partly in stromal cells including vascular endothelial cells and fibroblasts. Conclusion The up- regulated expression of Gremlin- 1 may be closely associated with the development of primary liver cancer and liver cirrhosis.
- Gremlin-1 /
- liver neoplasms /
- liver cirrhosis

HTML全文

参考文献(17)

[1]TOPOL LZ, MARX M, LAUGIER D, et al.Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture[J].Mol Cell Biol, 1997, 17 (8) :4801-4810.

[2]NICOLI S, GILARDELLI CN, POZZOLI O, et al.Regulated expression pattern of gremlin during zebrafish development[J].Gene Expr Patterns, 2005, 5 (4) :539-544.

[3]MICHOS O, PANMAN L, VINTERSTEN K, et al.Gremlin-mediated BMP antagonism induces the epithelial mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis[J].Development, 2004, 131 (14) :3401-3410.

[4]NAMKOONG H, SHIN SM, KIM HK, et al.The bone morphogenetic protein antagonist gremlin1 is overexpressed in human cancers and interacts with YWHAH protein[J].BMC Cancer, 2006, 18 (6) :74.

[5]SNEDDON JB, ZHEN HH, MONTGOMERY K, et al.Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation[J].Proc Natl Acad Sci U S A, 2006, 103 (40) :14842-14847.

[6]MULVIHILL MS, KWON YW, LEE S, et al.Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells[J].PLoS One, 2012, 7 (8) :e42264.

[7]KARAGIANNIS GS, BERK A, DIMITROMANOLAKIS A, et al.Enrichment map profiling of the cancer invasion front suggests regulation of colorectal cancerprogression by the bone morphogenetic protein antagonist, gremlin-1[J].Mol Oncol, 2013, 7 (4) :826-839.

[8]CHEN MH, YEH YC, SHYR YM, et al.Expression of gremlin 1correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors[J].J Gastroenterol, 2013, 48 (1) :101-108.

[9]KIM M, YOON S, LEE S, et al.Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion[J].PLoS One, 2012, 7 (4) :e35100.

[10]LAURILA R, PARKKILA S, ISOLA J, et al.The expression patterns of gremlin 1 and noggin in normal adult and tumor tissues[J].Int J Clin Exp Pathol, 2013, 6 (7) :1400-1408.

[11]SNEDDON J, ZHEN HH, MONTGOMERY K, et al.Bone morphogenic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation[J].PNAS, 2006, 103 (40) :14842-14847.

[12]ZHANG Y, ZHANG Q.Bone morphogenetic protein-7 and Gremlin:New emerging therapeutic targets for diabetic nephropathy[J].Biochem Biophys Res Commun, 2009, 383 (1) :1-3.

[13]FARKAS L, FARKAS D, GAULDIE J, et al.Transient overexpression of Gremlin results in epithelial activation and reversible fibrosis in rat lungs[J].Am J Respir Cell Mol Biol, 2011, 44 (6) :870-878.

[14]BOERS W, AARRASS S, LINTHORST C, et al.Transcriptional profiling reveals novel markers of liver fibrogenesis:Gremlin and Insulin-like growth factor-binding proteins[J].J Biol Chem, 2006, 281 (24) :16289-16295.

[15]STABILE H, MITOLA S, MORONI E, et al.Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor[J].Blood, 2007, 109 (5) :1834-1840.

[16]MACIEL TT, MELO RS, SCHOR N, et al.Gremlin promotes vascular smooth muscle cell proliferation and migration[J].J Mol Cell Cardiol, 2008, 44 (2) :370-379.

[17]LIU Y, WEN XM, LUI EL, et al.PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo by inhibiting VEGF signaling[J].Lab Invest, 2009, 89 (2) :209-221.

施引文献

资源附件(0)

访问统计