檢測同型半胱氨酸在不同分期胃癌患者血漿中的變化并初步探討其臨床意義

趙 妍，孫雅麗，張明暉，楊 艷，馬艷青，楊春潔，魏海波

內(nèi)蒙古醫(yī)科大學(xué)附屬赤峰醫(yī)院腫瘤內(nèi)三科，內(nèi)蒙古 赤峰 024000

檢測同型半胱氨酸在不同分期胃癌患者血漿中的變化并初步探討其臨床意義

趙 妍，孫雅麗，張明暉，楊 艷，馬艷青，楊春潔，魏海波

內(nèi)蒙古醫(yī)科大學(xué)附屬赤峰醫(yī)院腫瘤內(nèi)三科，內(nèi)蒙古 赤峰 024000

目的 檢測不同分期胃癌患者血漿中同型半胱氨酸(homocysteine, Hcy)水平，分析腫瘤分期與Hcy的關(guān)系，并初步探討其在胃癌患者中的臨床意義。方法 收集2013年9月-2014年10月就診于內(nèi)蒙古醫(yī)科大學(xué)附屬赤峰醫(yī)院經(jīng)病理學(xué)(胃鏡)確診的未行任何治療的胃癌患者為試驗組，對照組選自在我院體檢的健康成人。電化學(xué)發(fā)光方法檢測兩組人群血漿Hcy水平。并分析不同臨床分期胃癌患者血漿Hcy水平。結(jié)果 經(jīng)確診的60例胃癌患者中，Hcy升高者32例，平均(15.62±2.27)μmol/ml。對照組升高者2例，平均(10.25±2.01)μmol/ml，差異有統(tǒng)計學(xué)意義(P<0.01)。胃癌早期(Ⅰ期、Ⅱ期)血漿Hcy較健康成人升高(P<0.05)，但Ⅰ期與Ⅱ期比較，差異無統(tǒng)計學(xué)意義(P>0.05)；隨著腫瘤分期的升高，晚期患者(Ⅲ期、Ⅳ期)血漿Hcy升高明顯，Ⅲ期患者與Ⅰ期及Ⅱ期胃癌患者比較，差異均有統(tǒng)計學(xué)意義(P<0.05)；Ⅳ期患者與Ⅲ期比較，差異有統(tǒng)計學(xué)意義(P<0.05)。結(jié)論 Hcy有望作為胃癌的標(biāo)志物，輔助診斷、評價療效，監(jiān)測腫瘤復(fù)發(fā)。

胃癌；同型半胱氨酸；腫瘤分期

同型半胱氨酸(homocysteine, Hcy)是一種與半胱氨酸同系的四碳氨基酸，是蛋氨酸分解合成代謝的中間產(chǎn)物，本身不參與體內(nèi)蛋白質(zhì)的合成。在臨床上，Hcy主要應(yīng)用于心腦血管病危險性評估。國內(nèi)外也有報道，Hcy與腫瘤有一定的關(guān)系[1]，其在乳腺癌、結(jié)直腸癌、原發(fā)性肝細(xì)胞癌、惡性淋巴瘤、胃癌、卵巢癌、胰腺癌等多種惡性腫瘤患者的血漿中均有升高[2-5]。Hcy在胃癌患者血漿中有所升高，其升高水平與腫瘤分期是否有關(guān)，目前國內(nèi)外尚無報道。本研究通過檢測胃癌患者及健康成人血漿中Hcy水平，觀察Hcy的水平與腫瘤的分期是否有關(guān)。

1 資料與方法

1.1 一般資料收集2013年9月-2014年10月就診于內(nèi)蒙古醫(yī)科大學(xué)附屬赤峰醫(yī)院初次經(jīng)病理學(xué)(胃鏡)確診的未行任何治療的60例胃癌患者為試驗組，男38例，女22例，年齡50～60歲，平均年齡(55±31)歲。對照組選自健康體檢者，共60名，男38名，女22名，年齡50～60歲，平均年齡(54±4)歲。入選標(biāo)準(zhǔn)：年齡50～60歲，均經(jīng)問卷調(diào)查無吸煙史、無嗜酒史及喝咖啡習(xí)慣、無心腦血管疾病、無糖尿病，未服用過影響葉酸及Hcy代謝藥物的健康成人。將試驗組根據(jù)美國國立綜合癌癥網(wǎng)絡(luò)(NCCN)指南進(jìn)行臨床分期，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期為早期，Ⅲ～Ⅳ期為晚期。

1.2 血漿HCY測定清晨空腹，肘靜脈采血，我院檢驗科用電化學(xué)發(fā)光方法檢測(FPLA)檢測血漿中Hcy水平，正常值參考范圍為4.44～13.56 μmol/ml。

2 結(jié)果

2.1 胃癌患者與健康人比較經(jīng)確診的60例胃癌患者中，Hcy升高者32例，平均(15.62±2.27)μmol/ml。對照組60名健康人中，Hcy升高者2名，平均(10.25±2.01)μmol/ml。兩者相比，差異有統(tǒng)計學(xué)意義(P<0.01，見圖1)。

圖1 胃癌患者與健康人血漿同型半胱氨酸比較

2.2 不同分期胃癌患者血漿Hcy水平Ⅱ期患者血漿Hcy水平與Ⅰ期患者比較，差異無統(tǒng)計學(xué)意義(P>0.05)；Ⅰ期及Ⅱ期患者與健康人相比，差異有統(tǒng)計學(xué)意義(P<0.05)；Ⅲ期患者與Ⅰ期及Ⅱ期胃癌患者相比，差異均有統(tǒng)計學(xué)意義(P<0.05)；Ⅳ期患者與Ⅲ期比較，差異有統(tǒng)計學(xué)意義(P<0.05，見表1)。

表1 不同分期胃癌患者血漿同型半胱氨酸水平

3 討論

同型半胱氨酸(homocysteine，Hcy)是一種含硫氨基酸[6-7]，為蛋氨酸代謝的中間產(chǎn)物，在體內(nèi)經(jīng)蛋氨酸脫甲基化而生成，本身不參與體內(nèi)蛋白質(zhì)的合成。Hcy主要通過以下兩個途徑進(jìn)行分解代謝[8]：一是Hcy在胱硫醚合成酶(CBS)作用下以VitB6為輔助因子轉(zhuǎn)化為胱硫醚及半胱氨酸，最終分解為丙酮酸、硫酸和水；二是Hcy在葉酸、VitB12及亞甲基四氫葉酸還原酶(MTHFR)作用下甲基化形成蛋氨酸而參加蛋氨酸循環(huán)。葉酸、VitB6、VitB12缺乏或CBS基因、MTHFR基因突變，均可導(dǎo)致Hcy代謝和清除障礙，引起高Hcy血癥。

在臨床上，Hcy主要用于心腦血管病危險性的評估。目前，國內(nèi)外有報道，Hcy與腫瘤有一定的關(guān)系，在乳腺癌、結(jié)直腸癌、原發(fā)性肝細(xì)胞癌、惡性淋巴瘤、胃癌、宮頸癌等多種惡性腫瘤者血漿中均有升高[9-13]，其機制可能與葉酸的缺乏有關(guān)。葉酸為DNA合成及其甲基化提供一碳單位，對生長發(fā)育等功能有重要影響。對于腫瘤患者來說，如果葉酸特別是Ⅳ-甲基四氫葉酸缺乏，可導(dǎo)致蛋氨酸循環(huán)受阻，Hcy升高[14]，蛋氨酸水平下降，繼而致S-腺苷蛋氨酸下降。S-腺苷蛋氨酸降低可導(dǎo)致DNA甲基化程度降低，誘導(dǎo)原癌基因如c-myc、c-fos等的表達(dá)，最終導(dǎo)致腫瘤發(fā)生[15-17]。

本研究用電化學(xué)發(fā)光方法檢測胃癌患者與健康人血漿中Hcy水平，結(jié)果顯示胃癌患者較健康人血漿Hcy水平升高，差異有統(tǒng)計學(xué)意義。同時將收集的病例根據(jù)NCCN指南進(jìn)行分期，結(jié)果顯示，各期患者血漿Hcy水平與健康人相比，差異有統(tǒng)計學(xué)意義，Ⅱ期與Ⅰ期比較，差異無統(tǒng)計學(xué)意義，Ⅲ、Ⅳ期隨著分期的升高，血漿Hcy水平隨之升高。Hcy有望成為胃癌的標(biāo)志物，輔助診斷、評價療效，監(jiān)測腫瘤復(fù)發(fā)。

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(責(zé)任編輯：王豪勛)

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

趙妍，主治醫(yī)師，碩士，研究方向：腫瘤的綜合治療。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