结肠息肉患者血浆血管生成素-2水平检测的临床意义

引用本文

潘小成. 结肠息肉患者血浆血管生成素-2水平检测的临床意义. 检验医学, 2013, 28(6): 529-531
复制到剪切板

Permissions

结肠息肉患者血浆血管生成素-2水平检测的临床意义

潘小成

安吉县人民医院检验科,浙江安吉 313300

作者简介:潘小成,男,1970年生,学士,副主任技师,主要从事免疫和细胞形态学检验工作。

摘要

目的探讨血浆血管生成素-2 (Ang-2)水平在结肠息肉患者中的变化及临床意义。方法应用酶联免疫吸附试验(ELISA)检测91例结肠息肉患者术前、术后(1、5、9、13、17 d)血浆Ang-2水平,同时测定血浆癌抗原72-4(CA72-4)水平,并选择肠镜检查无病变患者30名作为对照组。结果结肠息肉组术前血浆Ang-2[(1 726.7±201.8) ng/L]、CA72-4[37.5(17.8~126.4)U/mL]水平均高于健康对照组[(1 087.5±174.3) ng/L]、6.1(1.5~10.27)U/mL](P<0.05);术后约10 d左右降至正常水平。结论结肠息肉患者术前血浆Ang-2水平较高,术后下降明显,Ang-2可以作为结肠息肉患者术后有效的监测指标之一。

关键词: 血管生成素-2; 癌抗原72-4; 结肠息肉

中图分类号:R446.62 文献标志码:A 文章编号:1673-8640(2013)06-0529-03

Show Figures

引言

结肠息肉是一类从黏膜表面突出到结肠肠腔内的隆起状物,易恶变为结肠癌,息肉切除后缺少有效的生物评价指标。息肉形成与新生血管有密切的联系,血管的形成包括内皮细胞的激活、迁徙和增生,受许多肽类和非肽类物质调节。目前研究表明,血管生成素在结肠息肉到癌变的进展中对癌血管的形成起到重要的作用^{[ 1]}。血管生成素家族是近年来逐渐被认识的一种较强的血管形成因子,血管生成素及其受体是近年来发现的血管生成调节因子,在血管生成中发挥重要作用^{[ 2]}。特别是血管生成素-1(Ang-1)、血管生成素-2(Ang-2)和表皮生长因子同源结构域的酪氨酸激酶-2 (Tie-2) 受体在胚胎血管发育、肿瘤^{[ 3, 4]}血管生成及转移、炎症反应等方面起重要作用。本研究通过检测结肠息肉患者术前、术后血浆Ang-2的水平变化,探讨Ang-2在结肠息肉患者术后的监测效果。

材料和方法

一、对象

收集安吉县人民医院2011年3月至2012年5月间术后经病理确诊无癌变结肠息肉患者91例,年龄(57±12)岁,肠镜检查无病变者30名作为对照组,年龄(55±9)岁。所有研究对象均排除肝肾功能异常、心脑血管病变和肿瘤等疾病。

二、方法

分别在术前、术后(1、5、9、13、17 d)抽取结肠息肉患者外周静脉血5 mL于抗凝管内,混匀后,1 800× g离心10 min,分离血浆,置-80 ℃冰箱保存待检。Ang-2测定采用酶联免疫吸附试验(ELISA)检测,检测试剂由Quantikine公司提供,严格按照说明书操作。CA72-4测定采用罗氏E170电化学发光仪器检测,试剂、质控品、定标液均为罗氏原装配套产品。

三、统计学方法

采用SPSS 13.0统计软件进行统计分析,Ang-2为正态分布资料,采用 ±s表示,2组间比较采用两独立样本 t检验,相关分析采用Spearman相关分析;CA72-4为非正态分布资料采用中位数(四分位数间距)表示,2组间比较采用两样本秩和检验。 P<0.05为差异有统计学意义。

结果

一、结肠息肉患者术前、术后及健康对照组血浆Ang-2和CA72-4水平检测结果

结肠息肉患者血浆Ang-2、CA72-4水平术前及术后1、9 d高于对照组( P<0.05),结果见表1。

表1 结肠息肉患者术前、术后及对照组血浆Ang-2和CA72-4水平比较

二、结肠息肉患者术后血浆Ang-2和CA72-4水平的变化

结肠息肉患者术后平均血浆Ang-2水平下降比CA72-4快,约10 d左右降至对照组水平,术后3~5 d血浆Ang-2浓度出现不降反升的现象;CA72-4则需要约20 d降至对照组水平,结果见图1。

	Figure Option View Download New Window
	图1 结肠息肉术后血浆Ang-2和CA72-4时间变化曲线注:(a)为CA72-4;(b)为Ang-2

讨论

结肠息肉患者早期症状轻微或者没有症状,内窥镜检查是结肠息肉诊断和治疗的最佳方法,但是息肉切除后缺乏有效的评价指标。本研究结果显示结肠息肉患者血浆Ang-2水平高于肠镜检查无病变体检者,王晋涛等^{[ 5]}研究发现肠腺瘤中Ang-2和VEGF表达高于正常组织,但低于肠腺癌,这些研究结果提示结肠息肉患者出现高水平Ang-2表达应引起足够的重视,可能与肿瘤恶变有关。Ang-2可以有效刺激血管内皮细胞增殖,诱导内皮细胞蛋白酶的产生,促进局部血管的形成^{[ 6]}。研究表明血浆Ang-2水平亦与多种肿瘤发生发展及预后密切相关^{[ 7]}。本研究结果显示,结肠息肉患者血浆CA72-4水平高于无病变体检者,且Ang-2和CA72-4存在一定相关性,但有差异。结肠息肉患者术后平均血浆Ang-2浓度下降比CA72-4快,约10 d左右降至对照组水平,这与李晓勇等^{[ 8]}报道相近。但是结肠息肉患者术后3~5 d血浆Ang-2浓度出现不降反升的现象,血浆CA72-4呈现逐渐下降趋势,两者间存在明显差异(见图1),这可能与手术刺激血管引起Ang-2分泌增加有关, Kong等^{[ 9]}报道手术诱导肿瘤血管生成,与本研究结果一致。刘少平等^{[ 10]}报道胃癌及术后随访患者血清Ang-2含量来评价手术及复发情况,该研究表明Ang-2有助于胃癌术后复发转移的监测及预后的评价,与本研究具有相似之处。本研究结果提示消化内镜医生在临床治疗结肠息肉,尤其是多发性和直径大者,手术前可检测血浆Ang-2,结合术后Ang-2表达变化决定综合治疗方案,对术后Ang-2表达异常者,制定密切随访时间表,缩短随访时间间隔,以便发现其他异常病变,可及时切除,防止息肉恶变,有重要的临床应用价值。

综上所述,血浆Ang-2水平诊断结肠息肉具有一定的敏感性和特异性,术后动态监测血浆Ang-2有利于发现异常病变,可以作为结肠息肉患者术后有效的监测指标之一,有着重要的临床应用价值。

The authors have declared that no competing interests exist.

参考文献

View Option

[1]	Shantha Kumara HM, Hoffman A, Kim IY, et al. Colorectal resection, both open and laparoscopic-assisted, in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels[J]. Surg Endosc, 2009, 23(2): 409-415. [本文引用:1] [JCR: 3.427]
[2]	Ahmed A, Fujisawa T. Multiple roles of angiopoietins in atherogenesis[J]. Curr Opin Lipidol, 2011, 22(5): 380-385. [本文引用:1] [JCR: 5.839]
[3]	万汝根, 陈德宝, 楼永刚, 等. 血清血管生成素2水平在胰腺癌诊断中的价值[J]. 中华肿瘤杂志, 2011, 33(1): 47-49. [本文引用:1]
[4]	李金明, 谢南, 龚义华, 等. Ang-2和Tne-2在肝癌中表达及血管生成关系的研究[J]. 检验医学, 2011, 26(3): 150-152. [本文引用:1]
[5]	王晋涛, 李晓杰, 邹益友. Ang-2和VEGF在大肠腺瘤中的表达及其临床意义[J]. 医学研究杂志, 2010, 39(7): 74-77. [本文引用:1]
[6]	Hu B, Cheng SY. Angiopoietin-2: development of inhibitors for cancer therapy[J]. Curr Oncol Rep, 2009, 11(2): 111-116. [本文引用:1] [JCR: 3.327]
[7]	Bach F, Uddin FJ, Burke D. Angiopoietins in malignancy[J]. Eur J Surg Oncol, 2007, 33(1): 7-15. [本文引用:1]
[8]	李晓勇, 刘少平. 结直肠癌患者血清Ang-2含量检测及意义[J]. 山东医药, 2010, 50(25): 31-32. [本文引用:1]
[9]	Kong B, Michalski CW, Friess H, et al. Surgical procedure as an inducer of tumor angiogenesis[J]. Exp Oncol, 2010, 32(3): 186-189. [本文引用:1] [JCR: 0.752]
[10]	刘少平, 胡亚华, 方春华, 等. 胃癌及术后随访患者血清血管生成素-2含量的临床意义[J]. 中华消化杂志, 2011, 31(8): 513-516. [本文引用:1]

2009

3.427

0.0

. 2009, 23(2):409-415 DOI:10.1007/s00464-008-0132-5

Colorectal resection, both open and laparoscopic-assisted, in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels

1.Columbia University College of Physicians & Surgeons Section of Colon & Rectal Surgery New York USA 2.The Wonju College of Medicine, Yonsei University Department of Surgery Wonju South Korea 3.Ferguson Clinic Division of Colon and Rectal Surgery Grand Rapids MI USA 4.Cleveland Clinic Department of Colon & Rectal Surgery Cleveland OH USA

Introduction

Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study’s purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels.

... 目前研究表明,血管生成素在结肠息肉到癌变的进展中对癌血管的形成起到重要的作用^[1] ...

2011

5.839

0.0

... 血管生成素家族是近年来逐渐被认识的一种较强的血管形成因子,血管生成素及其受体是近年来发现的血管生成调节因子,在血管生成中发挥重要作用^[2] ...

2011

0.0

2011

0.0

2010

0.0

... 本研究结果显示结肠息肉患者血浆Ang-2水平高于肠镜检查无病变体检者,王晋涛等^[5]研究发现肠腺瘤中Ang-2和VEGF表达高于正常组织,但低于肠腺癌,这些研究结果提示结肠息肉患者出现高水平Ang-2表达应引起足够的重视,可能与肿瘤恶变有关 ...

2009

3.327

0.0

. 2009, 11(2):111-116 DOI:10.1007/s11912-009-0017-3

Angiopoietin-2: development of inhibitors for cancer therapy

1.University of Pittsburgh Cancer Institute and Department of Pathology HCCLB, 2.26f, 5117 Centre Avenue Pittsburgh PA 15213 USA

Angiopoietin-2 (Ang2) is a member of the Ang family, which plays an important role in angiogenesis during the development and growth of human cancers. Ang2’s role in angiogenesis generally is considered as an antagonist for Ang1, inhibiting Ang1-promoted Tie2 signaling, which is critical for blood vessel maturation and stabilization. Ang2 modulates angiogenesis in a cooperative manner with another important angiogenic factor, vascular endothelial growth factor A. Genetic studies have revealed that Ang2 also is critical in lymphangiogenesis during development. However, new evidence suggests more complicated roles for Ang2 in angiogenesis in physiologic processes and invasive phenotypes of cancer cells during progression of human cancers. This article discusses recent studies of Ang2 in angiogenesis and the implication of Ang2 as a therapeutic target as well as a potential inhibitor for antiangiogenesis treatment for cancer patients.

... Ang-2可以有效刺激血管内皮细胞增殖,诱导内皮细胞蛋白酶的产生,促进局部血管的形成^[6] ...

2007

0.0

. 2007, 33(1):7-15 DOI:10.1016/j.ejso.2006.07.015

Angiopoietins in malignancy

<ul><li>Department of Academic Surgery, Room B40, Clarendon Wing, Leeds General Infirmary, Great George Street, Leeds, West Yorkshire LS1 3EX, UK</li></ul>

Background

Tumour growth is dependant upon the development of an adequate blood supply. This, in turn, is thought to depend upon a switch by the tumour, from a dormant to angiogenic state. Recent data suggest that this switch may occur when the balance of pro- and anti-angiogenic agents alters to promote angiogenesis. Angiopoietins may be involved in this balance.

Methods

An electronic literature search was performed with respect to angiopoietins from 1996 to the present. Published data from in-vitro and in-vivo studies were critically analysed. A specific focus was made of studies relating to tumour growth and vasculature.

Results

Since angiopoietin-1 was first described in 1996, three more angiopoietins have been described. All family members bind to the Tie-2 receptor. There is now a considerable accumulation of data that suggests they play a pivotal role in the development and stabilisation of tumour vasculature. angiopoietin-2 appears to be pro-angiogenic whilst angiopoietin-1 appears to be a stabilising factor.

Conclusions

Recent trials of anti-angiogenic agents show promise in the treatment of solid human cancers. The angiopoietins are a new family of proteins that appear to be influential in the development of the tumour vasculature. Manipulation of the angiopoietin balance may provide a potential therapeutic target in human cancer.

... 研究表明血浆Ang-2水平亦与多种肿瘤发生发展及预后密切相关^[7] ...

2010

0.0

... 结肠息肉患者术后平均血浆Ang-2浓度下降比CA72-4快,约10 d左右降至对照组水平,这与李晓勇等^[8]报道相近 ...

2010

0.752

0.0

... 但是结肠息肉患者术后3~5 d血浆Ang-2浓度出现不降反升的现象,血浆CA72-4呈现逐渐下降趋势,两者间存在明显差异(见图1),这可能与手术刺激血管引起Ang-2分泌增加有关, Kong等^[9]报道手术诱导肿瘤血管生成,与本研究结果一致 ...

2011

0.0

... 刘少平等^[10]报道胃癌及术后随访患者血清Ang-2含量来评价手术及复发情况,该研究表明Ang-2有助于胃癌术后复发转移的监测及预后的评价,与本研究具有相似之处 ...