徐偉，江鴻，郭燕菊，戴廣海

(1.解放軍醫(yī)學(xué)院，北京100853；2.中央軍委聯(lián)合參謀部警衛(wèi)局衛(wèi)生保健處)

·論著·

血清腫瘤壞死因子α和血管內(nèi)皮生長(zhǎng)因子與結(jié)直腸癌的相關(guān)性分析

徐偉1，江鴻2，郭燕菊2，戴廣海1

(1.解放軍醫(yī)學(xué)院，北京100853；2.中央軍委聯(lián)合參謀部警衛(wèi)局衛(wèi)生保健處)

目的探討結(jié)直腸癌患者術(shù)前血清腫瘤壞死因子α(TNF-α)及血管內(nèi)皮生長(zhǎng)因子(VEGF)水平與直腸癌臨床及病理特征的相關(guān)性。方法采用酶聯(lián)免疫吸附法(ELISA)檢測(cè)納入研究對(duì)象血清TNF-α，VEGF水平，比較結(jié)直腸癌患者與健康對(duì)照人群之間差異；分析TNF-α、VEGF與結(jié)直腸癌患者臨床及病理特征關(guān)系。結(jié)直腸癌組患者與健康對(duì)照組的血清細(xì)胞因子水平比較采用Mann-Whitney U檢驗(yàn)，細(xì)胞因子與臨床病理特征的相關(guān)性分析采用Mann-Whitney U和Knlskal-Wallis H方法。結(jié)果結(jié)直腸癌組和健康對(duì)照組血清VEGF表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05)，結(jié)直腸癌組血清TNF-α表達(dá)水平低于健康對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(Plt;0.001)。腫瘤直徑lt;5 cm患者血清VEGF表達(dá)水平低于直徑≥5 cm患者， TNF-α表達(dá)水平高于直徑≥5 cm患者(Plt;0.001)。結(jié)論結(jié)直腸癌患者術(shù)前血清TNF-α及VEGF水平對(duì)結(jié)直腸癌的診斷及腫瘤大小預(yù)測(cè)具有一定的臨床價(jià)值。

結(jié)直腸腫瘤；腫瘤壞死因子α；血管內(nèi)皮生長(zhǎng)因子類

結(jié)直腸癌是一種常見(jiàn)的惡性腫瘤，大約占人類癌癥的15%[1-3]。當(dāng)前的診斷技術(shù)和結(jié)腸鏡檢查使得結(jié)腸癌早期診斷較為容易，因此早期結(jié)腸癌治愈率相對(duì)較高，達(dá)80%～90%[4-6]。腫瘤壞死因子α(TNF-α)由巨噬細(xì)胞，單核細(xì)胞，嗜中性粒細(xì)胞分泌，是涉及全身炎癥的細(xì)胞因子，有廣泛的抗腫瘤和抗病毒生物活性[7-10]。血管內(nèi)皮生長(zhǎng)因子(VEGF)在上皮、間質(zhì)、特別是腫瘤細(xì)胞中大量產(chǎn)生。研究提示，VEGF的血清濃度升高與結(jié)直腸癌病變密切相關(guān)，并與疾病的臨床分期相關(guān)[11-12]。本研究將結(jié)直腸癌患者的術(shù)前血清TNF-α和VEGF水平與健康對(duì)照人群的血清細(xì)胞因子水平進(jìn)行比較，分析其在癌癥病變中的作用。

1 資料與方法

1.1 一般資料 收集2012年1月至2016年12月解放軍總醫(yī)院手術(shù)治療的146例經(jīng)病理學(xué)診斷證實(shí)為結(jié)直腸癌患者的臨床資料。其中男84例，女62例；年齡18～89歲，中位年齡63歲。所有患者術(shù)前均未進(jìn)行化療、放療、生物治療及其他抗腫瘤治療。另外收集50例同期健康體檢結(jié)果正常人員的血清作為健康對(duì)照組。

1.2 方法

1.2.1 血清采集 采集手術(shù)前7 d內(nèi)的患者外周靜脈血樣，并將其置于離心管中。血液樣本在室溫下放置30 min，并以2000 g離心10 min；血清被分離后，儲(chǔ)存在-70 ℃冰箱中，等待測(cè)定。

1.2.2 TNF-α、VEGF檢測(cè) 采用ELISA試劑盒檢測(cè)血清TNF-α、VEGF濃度。試劑盒由Abcam公司生產(chǎn)，嚴(yán)格按照產(chǎn)品說(shuō)明書(shū)操作。

2 結(jié)果

2.1 TNF-α和VEGF的表達(dá) 結(jié)直腸癌組患者的血清TNF-α低于健康對(duì)照組(Plt;0.001)；而結(jié)直腸癌組患者的血清VEGF與健康對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.073)。見(jiàn)表1。

表1 兩組的TNF-α和VEGF比較

2.2 TNF-α和VEGF與臨床參數(shù)的關(guān)系 TNF-α表達(dá)水平與腫瘤大小(≥5 cm者較低)(Plt;0.001)和腫瘤分化程度(分化程度低者較低)(Plt;0.001)有關(guān)；VEGF表達(dá)水平與腫瘤大小(lt;5 cm者較低)有關(guān)(Plt;0.001)，兩者與年齡、性別、原發(fā)性腫瘤、局部淋巴結(jié)均無(wú)顯著關(guān)聯(lián)(Pgt;0.05)。見(jiàn)表2。

3 討論

TNF-α具有腫瘤壞死和腫瘤促進(jìn)活性，可能通過(guò)誘導(dǎo)增殖、侵襲和轉(zhuǎn)移而參與致癌過(guò)程[8,13]。有研究表明口腔鱗狀細(xì)胞癌的唾液TNF-α表達(dá)水平顯著高于健康對(duì)照組[14]。本研究結(jié)果顯示，結(jié)直腸癌患者血清TNF-α水平低于健康對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義，腫瘤大于5 cm和腫瘤分化程度低者血清TNF-α水平低(Plt;0.001)，提示TNF-α在抑制結(jié)直腸癌的發(fā)生、發(fā)展中起著重要的作用，可用作結(jié)直腸癌預(yù)后的評(píng)估指標(biāo)。

表2 結(jié)直腸癌患者臨床參數(shù)與TNF-α和VEGF表達(dá)的關(guān)系

VEGF可誘導(dǎo)腫瘤血管分化及形成，是參與血管生發(fā)和成熟的重要條件[15-16]，同時(shí)也在腫瘤患者血管相關(guān)疾病中扮演重要角色[17]。VEGF可表達(dá)于正常組織，腫瘤細(xì)胞表達(dá)水平顯著增高[18]。但本研究表明結(jié)直腸癌組患者血清中的VEGF水平并不高于健康對(duì)照組，受腫瘤分化程度的影響也較小，僅腫瘤大于5 cm者血清VEGF濃度較高；本研究結(jié)果與文獻(xiàn)報(bào)道其他腫瘤的結(jié)果并不相同[19-20]，但也有研究表明頭頸部鱗癌和結(jié)直腸癌患者血清中的VEGF表達(dá)水平與健康對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義[21-22]。結(jié)直腸癌患者VEGF表達(dá)水平與腫瘤大小存在一定關(guān)聯(lián)，這與相關(guān)文獻(xiàn)報(bào)道[22]類似，這提示VEGF可能參與了結(jié)直腸癌的生長(zhǎng)和侵襲性轉(zhuǎn)移，并且可能與患者的預(yù)后相關(guān)。

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AcorrelationanalysisofTNF-α,VEGFandcolorectalcancer

XuWei*,JiangHong，GuoYanju,DaiGuanghai

(*MedicalCollegeofPLA,Beijing100853,China)

DaiGuanghai，Email：daigh301@vip.sina.com

ObjectiveTo explore the correlation between TNF-α or VEGF levels and clinicopathological features in patients with colorectal cancer.MethodsThe serum levels of TNF-α and VEGF were measured by enzyme-linked immunosorbent assay kits,and compared with healthy controls.The serum levels of cytokines of colorectal cancer patients and healthy controls were compared using Mann-Whitney U test,and the correlation between cytokines and clinicopathological features was analyzed using the Mann-Whitney U and Knlskal-Wallis H methods.ResultsThe serum level of VEGF in colorectal cancer patients had no significant difference from those in healthy control(Pgt;0.05).TNF-α in colorectal cancer patients was significantly lower than that of healthy control(Plt;0.001).The levels of VEGF and TNF-α significantly correlated with tumor size.ConclusionThe TNF-α and VEGF level of preoperative serum has clinical value for the diagnosis and predicted tumor size.

Colorectal neoplasms;Tumor necrosis factor-alpha；Vascular endothelial growth factors

吳階平醫(yī)學(xué)基金會(huì)臨床科研專項(xiàng)基金(320.6750.11076)

徐偉，主治醫(yī)師，Email：18910998563@189.cn

戴廣海，主任醫(yī)師，博士生導(dǎo)師，Email：daigh301@vip.sina.com

R735.3

A

10.3969/J.issn.1672-6790.2017.06.015

2017-07-20)