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中华肝脏外科手术学电子杂志 ›› 2013, Vol. 02 ›› Issue (03) : 175 -179. doi: 10.3877/cma.j.issn.2095-3232.2013.03.009

所属专题: 文献

临床研究

肝细胞肝癌患者血清和肝癌组织中fibulin-1蛋白的表达及其临床意义
傅斌生1, 刘炜2,(), 张剑文1, 台艳2, 易慧敏1, 张琪2, 杨扬1, 陈规划1   
  1. 1. 510630 广州,中山大学附属第三医院肝移植中心 中山大学器官移植研究所 广东省器官移植研究中心
    2. 广东省肝脏疾病研究重点实验室
  • 收稿日期:2013-03-22 出版日期:2013-06-10
  • 通信作者: 刘炜
  • 基金资助:
    国家重点基础研究发展计划(973计划)课题(2009CB522404); 国家十二五科技重大专项课题(2012ZX10002016-023,2012ZX10002017-005,2012ZX10002010-001-007); 国家自然科学基金(81000936,81172036); 教育部博士点基金(20100171120084,20100171120107); 广东省自然科学基金(S2012010008792); 中山大学重大项目(10ykjc03); 中山大学青年教师培育项目(10ykpy05)

Expression and clinical value of fibulin-1 protein in the serum and hepatocellular carcinoma tissues of patients with hepatocelluar carcinoma

Bin-sheng FU1, Wei LIU2,(), Jian-wen ZHANG1, Yan TAI2, Hui-min YI1, Qi ZHANG2, Yang YANG1, Gui-hua CHEN1   

  1. 1. Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Organ Transplantation Research Institute of Sun Yat-sen University, Organ Transplantation Research Center of Guangdong Province, Guangzhou 510630, China
  • Received:2013-03-22 Published:2013-06-10
  • Corresponding author: Wei LIU
  • About author:
    Corresponding author: LIU Wei, Email:
引用本文:

傅斌生, 刘炜, 张剑文, 台艳, 易慧敏, 张琪, 杨扬, 陈规划. 肝细胞肝癌患者血清和肝癌组织中fibulin-1蛋白的表达及其临床意义[J]. 中华肝脏外科手术学电子杂志, 2013, 02(03): 175-179.

Bin-sheng FU, Wei LIU, Jian-wen ZHANG, Yan TAI, Hui-min YI, Qi ZHANG, Yang YANG, Gui-hua CHEN. Expression and clinical value of fibulin-1 protein in the serum and hepatocellular carcinoma tissues of patients with hepatocelluar carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2013, 02(03): 175-179.

目的

探讨fibulin-1蛋白在肝细胞肝癌(肝癌)患者血清和肝癌组织中的表达水平及其临床意义。

方法

本前瞻性研究对象为2009年5月至2010年5月在中山大学附属第三医院行肝癌肝切除术,且经临床病理确诊为肝癌的40例患者(肝癌组)。患者均签署临床研究知情同意书,符合医学伦理学规定。肝癌组男36例,女4例;年龄(48±14)岁。另取同期在本院体检的48例健康人作为正常对照组(对照组)。肝癌组的血液样本于术前检查时抽取,对照组于体检时抽取。应用酶联免疫吸附试验检测血清fibulin-1蛋白水平。取8例肝癌患者的肝癌和癌旁组织,应用蛋白质印迹法检测fibulin-1蛋白相对含量。两组间的fibulin-1蛋白表达水平及肝癌组织和癌旁组织fibulin-1蛋白相对含量比较采用t检验。

结果

肝癌组患者血清fibulin-1蛋白表达水平为(44±8)mg/L,对照组为(30±9)mg/L,肝癌组血清fibulin-1蛋白表达水平明显高于对照组,差异有统计学意义(t=-7.02,P<0.05)。肝癌组肝癌及癌旁组织fibulin-1蛋白相对含量分别为0.65±0.25、0.24±0.06,两组差异有统计学意义(t=-2.70,P<0.05)。肝癌组患者血清fibulin-1蛋白表达水平与肿瘤血管浸润及肿瘤、淋巴、转移(TNM)分期相关(t=-6.12,-3.50;P<0.05),而与甲胎蛋白(AFP)含量、肿瘤大小和数目无关(t=-0.48,1.34,-1.29;P>0.05)。

结论

肝癌患者血清fibulin-1蛋白表达水平升高,肝癌组织的fibulin-1蛋白含量亦较癌旁组织升高,血清fibulin-1蛋白表达水平与血管浸润和TNM分期有关,fibulin-1蛋白可能参与肝癌的发生、发展。

Objective

To explore the expression and clinical value of fibulin-1 protein in the serum and tissues of hepatocellular carcinoma (HCC).

Methods

Forty HCC patients [36 males and 4 females; mean age of (48±14) years old] were enrolled in this prospective study. All the patients were diagnosed with HCC pathologically and received liver resection (HCC group) in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to May 2010. The informed consents of all patients were obtained and the ethical committee approval was received. Forty-eight healthy people received physical examinations in this hospital at the same period were enrolled as the control group. The serum specimens of HCC patients were collected before operation and the samples in the control group were collected during the physical examinations. The serum level of fibulin-1 was tested by enzyme-linked immune absorbent assay. The relative protein content of fibulin-1 in the HCC and para-carcinoma tissues of 8 patients with HCC were collected and tested using Western blot. The differences of expressive level of fibulin-1 protein and the relative content of fibulin-1 protein in HCC tissues and para-carcinoma tissues between 2 groups were compared using t test.

Results

The serum expressive level of fibulin-1 in HCC group [ (44±8) mg/L] was significantly higher than that in the control group[(30±9) mg/L] (t=-7.02, P<0.05) . The relative protein content of fibulin-1 in HCC tissues and the para-carcinoma tissues were 0.65±0.25, 0.24±0.06 respectively. Significant difference was observed(t=-2.70, P<0.05). The serum expressive level of fibulin-1 was related with tumor vascular invasion and the tumor, lymphatic, metastasis(TNM) staging (t=-6.12, -3.50; P<0.05), but not related with the alpha-fetalprotein (AFP) level, tumor size and numbers (t=-0.48, 1.34, -1.29; P>0.05).

Conclusions

The fibulin-1 expressive level in the serum of HCC patients rises, the protein content of fibulin-1 in the HCC tissues rises as well, compared with that in the para-carcinoma tissues. The serum expressive level of fibulin-1 is associated with the vascular invasion and TNM staging. Fibulin-1 protein may be involved in the occurrence and development of HCC.

图1 肝癌组8例患者肝癌组织和癌旁组织中的fibulin-1蛋白相对含量比较
表1 40例肝癌患者血清fibulin-1蛋白水平与临床病理学的参数关系(±s
[1]
Cheng YY, Jin H, Liu X, et al. Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer. Br J Cancer, 2008, 99(12):2083-2087.
[2]
Pupa SM, Argraves WS, Forti S, et al. Immunological and pathobiological roles of fibulin-1 in breast cancer. Oncogene,2004, 23(12):2153-2160.
[3]
Bardin A, Moll F, Margueron R, et al. Transcriptional and posttranscriptional regulation of fibulin-1 by estrogens leads to differential induction of messenger ribonucleic acid variants in ovarian and breast cancer cells. Endocrinology,2005, 146(2):760-768.
[4]
Wlazlinski A, Engers R, Hoffmann MJ, et al. Downregulation of several fibulin genes in prostate cancer. Prostate,2007, 67(16):1770-1780.
[5]
Timpl R, Sasaki T, Kostka G, et al. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol,2003, 4(6):479-489.
[6]
Weigell-Weber M, Sarra GM, Kotzot D, et al. Genomewide homozygosity mapping and molecular analysis of a candidate gene located on 22q13 (fibulin-1) in a previously undescribed vitreoretinal dystrophy. Arch Ophthalmol, 2003, 121(8):1184-1188.
[7]
Kubota Y, Kuroki R, Nishiwaki K. A fibulin-1 homolog interacts with an ADAM protease that controls cell migration in C. elegans. Curr Biol, 2004, 14(22):2011-2018.
[8]
Cangemi C, Skov V, Poulsen MK, et al. Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes. Clin Chem, 2011, 57(11):1556-1565.
[9]
Courtney HS, Li Y, Twal WO, et al. Serum opacity factor is a streptococcal receptor for the extracellular matrix protein fibulin-1. J Biol Chem, 2009, 284(19):12966-12971.
[10]
Piscaglia F, Dudás J, Knittel T, et al. Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells. Cell Tissue Res, 2009, 337(3):449-462.
[11]
Clinton GM, Rougeot C, Derancourt J, et al. Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells. Proc Natl Acad Sci U S A,1996, 93(1):316-320.
[12]
Qing J, Maher VM, Tran H, et al. Suppression of anchorage-independent growth and matrigel invasion and delayed tumor formation by elevated expression of fibulin-1D in human fibrosarcoma-derived cell lines. Oncogene, 1997, 15(18):2159-2168.
[13]
Hayashido Y, Lucas A, Rougeot C, et al. Estradiol and fibulin-1 inhibit motility of human ovarian- and breast-cancer cells induced by fibronectin. Int J Cancer,1998, 75(4):654-658.
[14]
Perbal B, Martinerie C, Sainson R, et al. The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling. Proc Natl Acad Sci U S A, 1999, 96(3):869-874.
[15]
Gallagher WM, Currid CA, Whelan LC. Fibulins and cancer: friend or foe? Trends Mol Med, 2005, 11(7):336-340.
[16]
Kuo PL, Shen KH, Hung SH, et al. CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF-κB/HDAC1 epigenetic regulation. Carcinogenesis, 2012, 33(12):2477-2487.
[17]
Kanda M, Nomoto S, Okamura Y, et al. Promoter hypermethylation of fibulin 1 gene is associated with tumor progression in hepatocellular carcinoma. Mol Carcinog, 2011, 50(8):571-579.
[18]
Argraves WS, Tanaka A, Smith EP, et al. Fibulin-1 and fibrinogen in human atherosclerotic lesions. Histochem Cell Biol, 2009, 132(5):559-565.
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