锌-α2-糖蛋白与胃肠癌及恶病质的相关性研究

Correlation between zinc-α2-glycoprotein and gastrointestinal cancer cachexia

目的：研究锌-α2-糖蛋白（ZAG）在胃肠癌病人与良性疾病病人体内的表达情况,以及在伴有恶病质与不伴有恶病质的胃肠癌病人体内的表达情况,分析ZAG与胃肠癌及其引起的恶病质状况的相关性。分析不同组织中ZAG的含量与血清、尿液中含量的相关性,探讨体内ZAG的主要来源。方法：选取我科2009年4月~10月的住院病人,分为肿瘤恶病质组、肿瘤非恶病质组以及良性对照组,各组均为40例。收集病人的血清、尿液、腹壁皮下脂肪组织及肿瘤组织4种标本,采用ELISA竞争法定量测定这4种标本中ZAG的含量,采用Western印迹法检测脂肪及肿瘤组织中ZAG的表达情况。所有数据利用SPSS 15.0软件进行分析。结果：胃肠癌病人血清及尿液中ZAG含量的均数分别为152.2μg/mL、158.3μg/mL,而良性对照组分别为27.1μg/mL与26.1μg/mL,两者差异显著（P〈0.001）。恶病质组病人血清、尿液及肿瘤组织中ZAG的含量均高于非恶病质组,差异有统计学意义,P值分别为0.010、0.022和0.005。在脂肪组织中,恶病质组的ZAG含量高于非恶病质组,但差异无统计学意义（P=0.060）。肿瘤组织中ZAG的含量与血清中的含量呈显著相关（r=0.735）,与尿液中含量的相关性较强（r=0.676）;脂肪组织中ZAG的含量与血清、尿液中含量的相关系数分别为0.457与0.534,呈一般相关。可见肿瘤、脂肪组织与体液中ZAG的含量均呈正相关,而肿瘤组织与体液的相关性更强。Western印迹法显示,胃肠癌病人两种组织中ZAG的表达均显著高于对照组。恶病质病人脂肪组织中ZAG的表达稍高于非恶病质病人,肿瘤组织中ZAG的表达明显高于非恶病质病人,说明恶病质状态下病人体内ZAG的表达明显上调,而肿瘤组织中增加的程度高于脂肪组织。结论：ZAG在胃肠癌病人体内的表达显著升高,在伴有恶病质的病人体内,其表达进一步升高。ZAG与胃肠癌及其引起的恶病质状态有明显的相关性。体液与组织中ZAG的含量有很强的相关性。肿瘤组织与体液中ZAG含量的相关性高于脂肪组织,胃肠癌病人体内ZAG的主要来源可能是肿瘤组织本身。

Objective Our study aims to analyze the association between zinc-α2-glycoprotein（ZAG） and cachexia from gastrointestinal cancer by comparing the expression of ZAG between patients with gastrointestinal cancer and without and between patients with cachexia and without.We study the main source of ZAG by analyzing the correlation between ZAG in different tissues and that in body fluids.Methods From Apr to Oct 2009,120 patients in the department of general surgery of Zhongshan Hospital were recruited and divided into three groups,including cancer cachexia group（n=40）,non-cachexia group（n=40） and control group（n=40）.Serum,urine,abdominal subcutaneous fat tissues and tumor tissues were collected.ZAG in these samples were quantitatively detected by ELISA.The expressions of ZAG protein in fat and tumor tissues were determined by Western blot.Results ZAG in serum and urine from patients with gastrointestinal cancer were 152.2 μg/mL and 158.3 μg/mL,which were significantly higher than those from control group（27.1 μg/mL and 26.1 μg/mL,respectively）,P〈0.001.The patients with cachexia had higher ZAG in serum,urine and tumor tissue than those without cachexia,P=0.010,P=0.022,P=0.005,respectively.ZAG in serum and urine was significantly correlated with that in tumor tissues（r= 0.735,r=0.676）,while correlated with that in fat tissue（r= 0.457,r=0.534）.The expression of ZAG protein in gastrointestinal cancer patients was significantly higher than that in control group,both in tumor and fat tissue.The expression of ZAG in tumor tissues from patients with cachexia was markedly higher than that from patients without cachexia and the difference was slight in fat tissue.Conclusions The expression of ZAG was elevated in patients with gastrointestinal cancer,and even more elevation was observed in patients with cachexia.ZAG expression strongly correlated with gastrointestinal cancer and cachexia.The stronger correlation between body fluids with tumor tissue than with fat tissue suggesting that tumor tissues may be the main source of ZAG in gastrointestinal cancer patients.