检测同型半胱氨酸在不同分期胃癌患者血浆中的变化并初步探讨其临床意义

赵 妍，孙雅丽，张明晖，杨 艳，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胃癌患者血浆中的变化并初步探讨其临床意义

赵 妍，孙雅丽，张明晖，杨 艳，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 检测不同分期胃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，并初步探讨其在胃癌患者中的临床意义。方法 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经病理学(胃镜)确诊的未行任何治疗的胃癌患者为试验组，对照组选自在我院体检的健康成人。电化学发光方法检测两组人群血浆Hcy水平。并分析不同临床分期胃癌患者血浆Hcy水平。结果 经确诊的60例胃癌患者中，Hcy升高者32例，平均(15.62±2.27)μmol/ml。对照组升高者2例，平均(10.25±2.01)μmol/ml，差异有统计学意义(P<0.01)。胃癌早期(Ⅰ期、Ⅱ期)血浆Hcy较健康成人升高(P<0.05)，但Ⅰ期与Ⅱ期比较，差异无统计学意义(P>0.05)；随着肿瘤分期的升高，晚期患者(Ⅲ期、Ⅳ期)血浆Hcy升高明显，Ⅲ期患者与Ⅰ期及Ⅱ期胃癌患者比较，差异均有统计学意义(P<0.05)；Ⅳ期患者与Ⅲ期比较，差异有统计学意义(P<0.05)。结论 Hcy有望作为胃癌的标志物，辅助诊断、评价疗效，监测肿瘤复发。

胃癌；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。在临床上，Hcy主要应用于心脑血管病危险性评估。国内外也有报道，Hcy与肿瘤有一定的关系[1]，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[2-5]。Hcy在胃癌患者血浆中有所升高，其升高水平与肿瘤分期是否有关，目前国内外尚无报道。本研究通过检测胃癌患者及健康成人血浆中Hcy水平，观察Hcy的水平与肿瘤的分期是否有关。

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(胃镜)确诊的未行任何治疗的60例胃癌患者为试验组，男38例，女22例，年龄50～60岁，平均年龄(55±31)岁。对照组选自健康体检者，共60名，男38名，女22名，年龄50～60岁，平均年龄(54±4)岁。入选标准：年龄50～60岁，均经问卷调查无吸烟史、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。将试验组根据美国国立综合癌症网络(NCCN)指南进行临床分期，其中Ⅰ期患者6例，Ⅱ期患者12例，Ⅲ期患者25例，Ⅳ期患者17例。Ⅰ～Ⅱ期为早期，Ⅲ～Ⅳ期为晚期。

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

2 结果

2.1 胃癌患者与健康人比较经确诊的60例胃癌患者中，Hcy升高者32例，平均(15.62±2.27)μmol/ml。对照组60名健康人中，Hcy升高者2名，平均(10.25±2.01)μmol/ml。两者相比，差异有统计学意义(P<0.01，见图1)。

图1 胃癌患者与健康人血浆同型半胱氨酸比较

2.2 不同分期胃癌患者血浆Hcy水平Ⅱ期患者血浆Hcy水平与Ⅰ期患者比较，差异无统计学意义(P>0.05)；Ⅰ期及Ⅱ期患者与健康人相比，差异有统计学意义(P<0.05)；Ⅲ期患者与Ⅰ期及Ⅱ期胃癌患者相比，差异均有统计学意义(P<0.05)；Ⅳ期患者与Ⅲ期比较，差异有统计学意义(P<0.05，见表1)。

表1 不同分期胃癌患者血浆同型半胱氨酸水平

3 讨论

同型半胱氨酸(homocysteine，Hcy)是一种含硫氨基酸[6-7]，为蛋氨酸代谢的中间产物，在体内经蛋氨酸脱甲基化而生成，本身不参与体内蛋白质的合成。Hcy主要通过以下两个途径进行分解代谢[8]：一是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；二是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。

在临床上，Hcy主要用于心脑血管病危险性的评估。目前，国内外有报道，Hcy与肿瘤有一定的关系，在乳腺癌、结直肠癌、原发性肝细胞癌、恶性淋巴瘤、胃癌、宫颈癌等多种恶性肿瘤者血浆中均有升高[9-13]，其机制可能与叶酸的缺乏有关。叶酸为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[14]，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[15-17]。

本研究用电化学发光方法检测胃癌患者与健康人血浆中Hcy水平，结果显示胃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NCCN指南进行分期，结果显示，各期患者血浆Hcy水平与健康人相比，差异有统计学意义，Ⅱ期与Ⅰ期比较，差异无统计学意义，Ⅲ、Ⅳ期随着分期的升高，血浆Hcy水平随之升高。Hcy有望成为胃癌的标志物，辅助诊断、评价疗效，监测肿瘤复发。

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(责任编辑：王豪勋)

Detection of homocysteine in the plasma of gastric cancer patients at different stages and its clinical significance

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

Department of N0.3 Oncology, Chifeng Hospital of Affiliated Inner Mongolia Medical University, Chifeng 024000, China

Objective To detect the homocysteine (Hcy) in the plasma of gastric cancer patients at different stages, to analyze the relationship between tumor stages and Hcy, and to investigate its clinical significance.Methods The patients with gastric cancer 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 adults that physical examination from our hospital were selected as control group. The Hcy level of plasma was detected by electrochemiluminescence methods. The Hcy levels at different clinical stages of gastric cancer patients were analyzed.Results There were 32 cases increased Hcy in 60 cases of gastric cancer, average of (15.62±2.27) μmol/ml, 2 cases increased Hcy in 60 healthy adults, average of (10.25±2.01) μmol/ml, and there was significant difference (P<0.01). Compared with healthy adults, in the early stage of gastric cancer (stage Ⅰ, stage Ⅱ), the Hcy increased (P<0.05), but there was no significant difference between phase I and phase Ⅱ (P>0.05). With increasing the staging of tumor, the momolysteine of advanced stage of gastric cancer (stage Ⅲ, stage Ⅳ) significantly increased. Compared with stage I and stage Ⅱ, there was statistically significant in stage Ⅲ (P<0.05). There was statistical significance between stage Ⅲ and stage Ⅳ (P<0.05).Conclusion Hcy is expected to as gastric cancer markers, it can auxiliary diagnosis, evaluate curative effect and monitor tumor recurrence.

Gastric cancer; Homocysteine; Tumor staging

赵妍，主治医师，硕士，研究方向：肿瘤的综合治疗。E-mail：zhaoyan198642@163.com

10.3969/j.issn.1006-5709.2016.01.007

R735.2

A

1006-5709(2016)01-0029-03

2015-06-09