徐伟，江鸿，郭燕菊，戴广海

(1.解放军医学院，北京100853；2.中央军委联合参谋部警卫局卫生保健处)

·论著·

血清肿瘤坏死因子α和血管内皮生长因子与结直肠癌的相关性分析

徐伟1，江鸿2，郭燕菊2，戴广海1

(1.解放军医学院，北京100853；2.中央军委联合参谋部警卫局卫生保健处)

目的探讨结直肠癌患者术前血清肿瘤坏死因子α(TNF-α)及血管内皮生长因子(VEGF)水平与直肠癌临床及病理特征的相关性。方法采用酶联免疫吸附法(ELISA)检测纳入研究对象血清TNF-α，VEGF水平，比较结直肠癌患者与健康对照人群之间差异；分析TNF-α、VEGF与结直肠癌患者临床及病理特征关系。结直肠癌组患者与健康对照组的血清细胞因子水平比较采用Mann-Whitney U检验，细胞因子与临床病理特征的相关性分析采用Mann-Whitney U和Knlskal-Wallis H方法。结果结直肠癌组和健康对照组血清VEGF表达水平差异无统计学意义(Pgt;0.05)，结直肠癌组血清TNF-α表达水平低于健康对照组，差异有统计学意义(Plt;0.001)。肿瘤直径lt;5 cm患者血清VEGF表达水平低于直径≥5 cm患者， TNF-α表达水平高于直径≥5 cm患者(Plt;0.001)。结论结直肠癌患者术前血清TNF-α及VEGF水平对结直肠癌的诊断及肿瘤大小预测具有一定的临床价值。

结直肠肿瘤；肿瘤坏死因子α；血管内皮生长因子类

结直肠癌是一种常见的恶性肿瘤，大约占人类癌症的15%[1-3]。当前的诊断技术和结肠镜检查使得结肠癌早期诊断较为容易，因此早期结肠癌治愈率相对较高，达80%～90%[4-6]。肿瘤坏死因子α(TNF-α)由巨噬细胞，单核细胞，嗜中性粒细胞分泌，是涉及全身炎症的细胞因子，有广泛的抗肿瘤和抗病毒生物活性[7-10]。血管内皮生长因子(VEGF)在上皮、间质、特别是肿瘤细胞中大量产生。研究提示，VEGF的血清浓度升高与结直肠癌病变密切相关，并与疾病的临床分期相关[11-12]。本研究将结直肠癌患者的术前血清TNF-α和VEGF水平与健康对照人群的血清细胞因子水平进行比较，分析其在癌症病变中的作用。

1 资料与方法

1.1 一般资料 收集2012年1月至2016年12月解放军总医院手术治疗的146例经病理学诊断证实为结直肠癌患者的临床资料。其中男84例，女62例；年龄18～89岁，中位年龄63岁。所有患者术前均未进行化疗、放疗、生物治疗及其他抗肿瘤治疗。另外收集50例同期健康体检结果正常人员的血清作为健康对照组。

1.2 方法

1.2.1 血清采集 采集手术前7 d内的患者外周静脉血样，并将其置于离心管中。血液样本在室温下放置30 min，并以2000 g离心10 min；血清被分离后，储存在-70 ℃冰箱中，等待测定。

1.2.2 TNF-α、VEGF检测 采用ELISA试剂盒检测血清TNF-α、VEGF浓度。试剂盒由Abcam公司生产，严格按照产品说明书操作。

2 结果

2.1 TNF-α和VEGF的表达 结直肠癌组患者的血清TNF-α低于健康对照组(Plt;0.001)；而结直肠癌组患者的血清VEGF与健康对照组差异无统计学意义(P=0.073)。见表1。

表1 两组的TNF-α和VEGF比较

2.2 TNF-α和VEGF与临床参数的关系 TNF-α表达水平与肿瘤大小(≥5 cm者较低)(Plt;0.001)和肿瘤分化程度(分化程度低者较低)(Plt;0.001)有关；VEGF表达水平与肿瘤大小(lt;5 cm者较低)有关(Plt;0.001)，两者与年龄、性别、原发性肿瘤、局部淋巴结均无显著关联(Pgt;0.05)。见表2。

3 讨论

TNF-α具有肿瘤坏死和肿瘤促进活性，可能通过诱导增殖、侵袭和转移而参与致癌过程[8,13]。有研究表明口腔鳞状细胞癌的唾液TNF-α表达水平显著高于健康对照组[14]。本研究结果显示，结直肠癌患者血清TNF-α水平低于健康对照组，差异有统计学意义，肿瘤大于5 cm和肿瘤分化程度低者血清TNF-α水平低(Plt;0.001)，提示TNF-α在抑制结直肠癌的发生、发展中起着重要的作用，可用作结直肠癌预后的评估指标。

表2 结直肠癌患者临床参数与TNF-α和VEGF表达的关系

VEGF可诱导肿瘤血管分化及形成，是参与血管生发和成熟的重要条件[15-16]，同时也在肿瘤患者血管相关疾病中扮演重要角色[17]。VEGF可表达于正常组织，肿瘤细胞表达水平显著增高[18]。但本研究表明结直肠癌组患者血清中的VEGF水平并不高于健康对照组，受肿瘤分化程度的影响也较小，仅肿瘤大于5 cm者血清VEGF浓度较高；本研究结果与文献报道其他肿瘤的结果并不相同[19-20]，但也有研究表明头颈部鳞癌和结直肠癌患者血清中的VEGF表达水平与健康对照组差异无统计学意义[21-22]。结直肠癌患者VEGF表达水平与肿瘤大小存在一定关联，这与相关文献报道[22]类似，这提示VEGF可能参与了结直肠癌的生长和侵袭性转移，并且可能与患者的预后相关。

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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

吴阶平医学基金会临床科研专项基金(320.6750.11076)

徐伟，主治医师，Email：18910998563@189.cn

戴广海，主任医师，博士生导师，Email：daigh301@vip.sina.com

R735.3

A

10.3969/J.issn.1672-6790.2017.06.015

2017-07-20)