检测同型半胱氨酸在不同分期结肠癌患者血浆中的变化

孙雅丽，赵 妍，杨 艳，张明晖，马艳青，杨春洁，魏海波

内蒙古医科大学附属赤峰医院肿瘤内三科，内蒙古 赤峰 024000

检测同型半胱氨酸在不同分期结肠癌患者血浆中的变化

孙雅丽，赵 妍，杨 艳，张明晖，马艳青，杨春洁，魏海波

内蒙古医科大学附属赤峰医院肿瘤内三科，内蒙古 赤峰 024000

目的 检测不同分期结肠癌患者血浆中同型半胱氨酸(homocysteine,Hcy)水平，分析肿瘤分期与Hcy的关系,并初步探讨其在结肠癌患者中的临床意义。方法 选取2013年9月-2014年10月就诊于内蒙古医科大学附属赤峰医院经病理学(结肠镜)确诊的未行任何治疗的结肠癌患者为试验组，选取同期健康体检者为对照组。电化学发光方法检测试验组及对照组血浆Hcy水平。结果 经确诊的80例结肠癌患者中，Hcy升高者26例，平均值为(14.62±3.24)μmol/ml。对照组80名健康人中，升高者2名，平均值为(10.25±2.01)μmol/ml。两者相比较,差异有显著性统计学意义(P<0.01)。在Hcy升高的结肠癌患者中，随着肿瘤分期的升高，Hcy随之升高，差异有统计学意义(P<0.01)。结论 对于确诊结肠癌的患者，Hcy有望成为结肠癌的标志物，能够辅助诊断、评价疗效、监测肿瘤复发。

结肠癌；同型半胱氨酸；肿瘤分期

同型半胱氨酸(homocysteine,Hcy)是一种与半胱氨酸同系的四碳氨基酸，是蛋氨酸分解合成代谢的中间产物，本身不参与体内蛋白质的合成[1]。在临床上，Hcy主要应用于心脑血管病危险性的评估。国内外也有报道，Hcy与肿瘤有一定的关系[3]，其在乳腺癌、结直肠癌、原发性肝细胞癌、恶性淋巴瘤、胃癌、卵巢癌、胰腺癌等多种恶性肿瘤患者的血浆中均有升高[2-7]。Hcy在结肠癌患者血浆中有所升高，其升高水平与肿瘤分期是否有关，目前国内外鲜有报道。本研究通过检测结肠癌患者及健康成人血浆中Hcy水平，验证结肠癌患者体内有Hcy升高，进一步将Hcy升高的结肠癌患者进行临床分期，观察Hcy水平与肿瘤分期是否有关。

1 资料与方法

1.1 一般资料 收集2013年9月-2014年10月就诊于内蒙古医科大学附属赤峰医院初次经病理学(结肠镜)确诊的未行任何治疗的结肠癌患者80例为试验组，年龄50～60岁，男48例，女32例。对照组选自本院体检的健康成人，共80名，男48名，女32名。纳入标准：年龄50～60岁；无吸烟史、无嗜酒史及喝咖啡习惯、无心脑血管疾病、无糖尿病；未服用过影响叶酸及Hcy代谢药物的健康成人。将试验组根据Dukes分期系统[8]进行分期，其中Dukes Ⅰ期16例，Dukes Ⅱ期30例，Dukes Ⅲ期患者24例，Dukes Ⅳ期10例。

1.2 血浆Hcy测定 清晨空腹，肘静脉采血，由检验科用电化学发光方法检测(FPLA)检测血浆中Hcy水平，Hcy正常值参考范围4.44～13.56 μmol/ml。

1.3 统计学分析 采用SPSS 10.0统计软件进行分析，显著性比较采用t检验，P<0.01为差异有统计学意义。

2 结果

2.1 两组Hcy水平比较 经确诊的80例结肠癌患者中，Hcy升高者26例，平均值为(14.62±3.24)μmol/ml。对照组的80名健康人中，升高者2例，平均值为(10.25±2.01)μmol/ml。两者相比，差异有显著性统计学意义(P<0.01，见图1)。

图1 结肠患者与健康人血浆Hcy水平Fig 1 Levels of plasma Hcy in colon cancer patients and healthy controls

2.2 不同分期结肠癌患者血浆Hcy水平 Dukes Ⅱ期结肠癌患者Hcy水平较Dukes Ⅰ期升高，差异有统计学意义(P<0.01)；Dukes Ⅲ期与Dukes Ⅱ、Dukes Ⅰ期比较，差异有统计学意义(P<0.01)；Dukes Ⅳ期较Dukes Ⅲ、Dukes Ⅱ、Dukes Ⅰ期升高，差异有统计学意义(P<0.01，见表1)。

表1 不同分期结肠癌患者血浆Hcy水平比较 ±s)Tab 1 Comparison of plasma Hcy levels in patients with colon cancer in different stages ±s)

3 讨论

Hcy主要通过下面两个途径进行分解代谢[9]：(1) Hcy在胱硫醚合成酶 (CBS) 作用下以 VitB6 为辅助因子转化为胱硫醚及半胱氨酸，最终分解为丙酮酸、 硫酸和水；(2) Hcy 在叶酸、 VitB12及亚甲基四氢叶酸还原酶 (MTHFR)作用下甲基化形成蛋氨酸而参加蛋氨酸循环。叶酸、VitB6、 VitB12缺乏或CBS 基因、MTHFR 基因突变，均可导致 Hcy 代谢和清除障碍，引起高Hcy血症。

叶酸是DNA合成及其甲基化提供一碳单位，对生长发育等功能有重要影响。对于肿瘤患者来说，如果叶酸特别是Ⅳ-甲基四氢叶酸缺乏，可导致蛋氨酸循环受阻，Hcy升高[10]，蛋氨酸水平下降；继而致S-腺苷蛋氨酸下降。S-腺苷蛋氨酸降低可导致DNA甲基化程度降低，诱导原癌基因如 c-myc、 c-fos 等的表达，最终导致肿瘤发生[11-12]。

本研究用FPLA检测血浆中Hcy水平比较结肠癌患者与健康人，结果显示结肠癌患者较健康人血浆Hcy水平升高，差异有统计学意义。同时将收集的病例根据Dukes系统进行分期，结果显示，在Hcy升高的结肠癌患者中，随着肿瘤分期的升高，Hcy随之升高，差异有统计学意义。同型半胱氨酸有望成为结肠癌的标志物，能够辅助诊断、评价疗效、监测肿瘤复发。

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Changes of homocysteine in the plasma of colon cancer patients in different stages

SUN Yali,ZHAO Yan,YANG Yan,ZHANG Minghui,MA Yanqing,YANG Chunjie,WEI Haibo

Department of NO.3 Oncology,Chifeng Hospital of Affiliated Inner Mongolia Medical University,Chifeng 024000,China

Objective To detect the changes of homocysteine (Hcy) in the plasma of colon cancer patients in different stages,to analyze the relationship between tumor stages and Hcy,and to explore its clinical significance. Methods Colon cancer patients diagnosed by pathology (endoscopy) without any treatment in Chifeng Hospital of Affiliated Inner Mongolia Medical University from Jun. 2013 to Oct. 2014 were collected as experiment group,healthy people as controls group. Hcy levels in plasma of the experiment group and the control group were collected by electrochemiluminescence methods. Results There were 26 cases with increased Hcy in 80 cases of colon cancer,average level of Hcy was (14.62±3.24) μmol/ml. There were 2 cases with increased Hcy in 80 healthy people,average level of Hcy was (10.25±2.01) μmol/ml (P<0.01). In the colon cancer patients that Hcy elevated,with increasing the staging of tumor,the level of Hcy in plasma was increasing,there was statistically significant (P<0.01). Conclusion For patients with colon cancer,Hcy is expected as colon cancer markers which could auxiliary diagnose,evaluate curative effect and monitor tumor recurrence.

Colon cancer; Homocysteine; Tumor staging

10.3969/j.issn.1006-5709.2016.02.009

孙雅丽，主任医师，研究方向：肿瘤内科的综合治疗

赵妍，主治医师，研究方向：胃肠道肿瘤、肺癌的内科治疗。E-mail: zhaoyan198642@163.com

R735.3+5

A

1006-5709(2016)02-0153-02

2015-06-30