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