血清腫瘤壞死因子α和血管內皮生長因子與結直腸癌的相關性分析

徐偉，江鴻，郭燕菊，戴廣海

(1.解放軍醫學院，北京100853；2.中央軍委聯合參謀部警衛局衛生保健處)

·論著·

血清腫瘤壞死因子α和血管內皮生長因子與結直腸癌的相關性分析

徐偉1，江鴻2，郭燕菊2，戴廣海1

(1.解放軍醫學院，北京100853；2.中央軍委聯合參謀部警衛局衛生保健處)

目的探討結直腸癌患者術前血清腫瘤壞死因子α(TNF-α)及血管內皮生長因子(VEGF)水平與直腸癌臨床及病理特征的相關性。方法采用酶聯免疫吸附法(ELISA)檢測納入研究對象血清TNF-α，VEGF水平，比較結直腸癌患者與健康對照人群之間差異；分析TNF-α、VEGF與結直腸癌患者臨床及病理特征關系。結直腸癌組患者與健康對照組的血清細胞因子水平比較采用Mann-Whitney U檢驗，細胞因子與臨床病理特征的相關性分析采用Mann-Whitney U和Knlskal-Wallis H方法。結果結直腸癌組和健康對照組血清VEGF表達水平差異無統計學意義(Pgt;0.05)，結直腸癌組血清TNF-α表達水平低于健康對照組，差異有統計學意義(Plt;0.001)。腫瘤直徑lt;5 cm患者血清VEGF表達水平低于直徑≥5 cm患者， TNF-α表達水平高于直徑≥5 cm患者(Plt;0.001)。結論結直腸癌患者術前血清TNF-α及VEGF水平對結直腸癌的診斷及腫瘤大小預測具有一定的臨床價值。

結直腸腫瘤；腫瘤壞死因子α；血管內皮生長因子類

結直腸癌是一種常見的惡性腫瘤，大約占人類癌癥的15%[1-3]。當前的診斷技術和結腸鏡檢查使得結腸癌早期診斷較為容易，因此早期結腸癌治愈率相對較高，達80%～90%[4-6]。腫瘤壞死因子α(TNF-α)由巨噬細胞，單核細胞，嗜中性粒細胞分泌，是涉及全身炎癥的細胞因子，有廣泛的抗腫瘤和抗病毒生物活性[7-10]。血管內皮生長因子(VEGF)在上皮、間質、特別是腫瘤細胞中大量產生。研究提示，VEGF的血清濃度升高與結直腸癌病變密切相關，并與疾病的臨床分期相關[11-12]。本研究將結直腸癌患者的術前血清TNF-α和VEGF水平與健康對照人群的血清細胞因子水平進行比較，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月解放軍總醫院手術治療的146例經病理學診斷證實為結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。所有患者術前均未進行化療、放療、生物治療及其他抗腫瘤治療。另外收集50例同期健康體檢結果正常人員的血清作為健康對照組。

1.2 方法

1.2.1 血清采集 采集手術前7 d內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，儲存在-70 ℃冰箱中，等待測定。

1.2.2 TNF-α、VEGF檢測 采用ELISA試劑盒檢測血清TNF-α、VEGF濃度。試劑盒由Abcam公司生產，嚴格按照產品說明書操作。

2 結果

2.1 TNF-α和VEGF的表達 結直腸癌組患者的血清TNF-α低于健康對照組(Plt;0.001)；而結直腸癌組患者的血清VEGF與健康對照組差異無統計學意義(P=0.073)。見表1。

表1 兩組的TNF-α和VEGF比較

2.2 TNF-α和VEGF與臨床參數的關系 TNF-α表達水平與腫瘤大小(≥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；VEGF表達水平與腫瘤大小(lt;5 cm者較低)有關(Plt;0.001)，兩者與年齡、性別、原發性腫瘤、局部淋巴結均無顯著關聯(Pgt;0.05)。見表2。

3 討論

TNF-α具有腫瘤壞死和腫瘤促進活性，可能通過誘導增殖、侵襲和轉移而參與致癌過程[8,13]。有研究表明口腔鱗狀細胞癌的唾液TNF-α表達水平顯著高于健康對照組[14]。本研究結果顯示，結直腸癌患者血清TNF-α水平低于健康對照組，差異有統計學意義，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在抑制結直腸癌的發生、發展中起著重要的作用，可用作結直腸癌預后的評估指標。

表2 結直腸癌患者臨床參數與TNF-α和VEGF表達的關系

VEGF可誘導腫瘤血管分化及形成，是參與血管生發和成熟的重要條件[15-16]，同時也在腫瘤患者血管相關疾病中扮演重要角色[17]。VEGF可表達于正常組織，腫瘤細胞表達水平顯著增高[18]。但本研究表明結直腸癌組患者血清中的VEGF水平并不高于健康對照組，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；本研究結果與文獻報道其他腫瘤的結果并不相同[19-20]，但也有研究表明頭頸部鱗癌和結直腸癌患者血清中的VEGF表達水平與健康對照組差異無統計學意義[21-22]。結直腸癌患者VEGF表達水平與腫瘤大小存在一定關聯，這與相關文獻報道[22]類似，這提示VEGF可能參與了結直腸癌的生長和侵襲性轉移，并且可能與患者的預后相關。

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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

吳階平醫學基金會臨床科研專項基金(320.6750.11076)

徐偉，主治醫師，Email：18910998563@189.cn

戴廣海，主任醫師，博士生導師，Email：daigh301@vip.sina.com

R735.3

A

10.3969/J.issn.1672-6790.2017.06.015

2017-07-20)