锌-α2-糖蛋白与胃肠癌及恶病质的相关性研究
摘要
目的：研究ZAG在胃肠癌患者与良性疾病患者体内的表达情况,以及在伴有恶病质与不伴有恶病质的胃肠癌患者体内的表达情况。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,推测体内ZAG的主要来源。
方法：选取复旦大学附属中山医院普外科2009年4月～10月的住院患者,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。要求恶性肿瘤病例为首次诊断的原发性胃肠癌,术前未经治疗,术后经病理确诊。恶病质组的入组标准为患者体重在3月内下降5%以上,或在6月内下降10%以上。收集患者的血清、尿液、腹壁皮下脂肪组织及肿瘤组织四种标本,采用ELISA竞争法定量测定这四种标本中ZAG的含量,采用Western Blot法检测脂肪及肿瘤组织中ZAG的表达情况。所有数据利用SPSS15.0软件进行分析。
结果：本实验入选120名病例,包括男性67名,女性53名,年龄在31～86岁,民族均为汉族。恶性肿瘤病例包括45例胃癌、22例结肠癌以及13例直肠癌,病理均为腺癌。良性对照组包括14例腹外疝、22例胆囊结石、3例胆囊息肉以及1例脾囊肿。三组病例间的性别比例以及年龄无统计学差异。
胃肠癌患者(包括恶病质与非恶病质)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27.1μ/ml与26.1μg／ml,两者差异显著(P<0.001)。恶病质组患者血清、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,但差异无显著性(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(1-=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。
免疫印迹显示,胃肠癌患者两种组织中ZAG的表达均显著高于对照组。恶病质患者脂肪组织中ZAG的表达稍高于非恶病质患者,肿瘤组织中ZAG的表达明显高于非恶病质患者,说明恶病质状态下患者体内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：与前列腺癌、乳腺癌类似,ZAG在胃肠癌患者体内的表达显著升高,在伴有恶病质的患者体内,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,胃肠癌患者体内ZAG的主要来源可能是肿瘤组织本身。
Objective To study the expression of ZAG in patients with or without gastrointestinal cancer and those with or without cachexia. To analyze the relationship between ZAG and gastrointestinal cancer cachexia. To analyze the correlation of ZAG in different tissues and body fluids, and to infer the principle source of ZAG.
Methods From April to October 2009,120 inpatients in the general surgery department of Zhongshan Hospital Affiliated to Fudan University were selected and divided into three groups, including cancer cachexia group(n=40), non-cachexia group(n=40) and control group(n=40).Patients with gastrointestinal cancer were diagnosed for the first time not receiving any preoperative treatments, and confirmed by pathological examination after operations.Patients with cachexia should have lost 5% of their weight in three months, or 10% in six months at least. Four samples, including serum, urine, abdominal subcutaneous fat tissue and tumor tissue, were collected. The contents of ZAG in these samples were quantitatively detected by ELISA respectively. The expressions of ZAG in fat and tumor tissues were detected by Western Blot. SPSS 15.0 was used for statistic analysis.
Results There were 67 males and 53 females in the 120 patients who were between the age of 31 and 86, and all of them belong to Han nationality. All cancer cases were pathological diagnosed as adenocarcinoma, including 45 gastric carcinoma,22 colon carcinoma and 13 rectal carcinoma. The control cases were 14 abdominal external hernia patients,22 cholecystolithiasis patients,3 cholecystic polips patients, and 1 splenic cyst patient aswell.The sex proportion and ages in three groups had no statistic differences.
The average content of ZAG in serum and urine of patients with gastrointestinal cancer were 152.2μg/ml and 158.3μg/ml, significantly higher than those in benign diseases, which were 27.1μg/ml and 26.1μg/ml,respectively (P<0.001).The patients with cachexia had higher levels of ZAG in serum, urine and tumor tissue than those without, with the P value 0.010,0.022 and 0.005 respectively, while in fat tissue there was no significant difference (P=0.060).
The content of ZAG in tumor tissue had a strong correlation with serum and urine with correlation coefficients of 0.735 and 0.676 respectively, while in fat tissue the correlation coefficient were 0.457 and 0.534 respectively. It was thus clear that the content of ZAG in tissues had a positive relationship with body fluids, and it was much stronger in tumor tissue.
Western Blot showed that the expression of ZAG in gastrointestinal cancer patients was markedly increased compare to those in control group both in tumor and fat tissue.The expression of ZAG in patients with cachexia was slightly higher than those without cachexia in fat tissue, while in tumor tissue the difference was much more evident. It illustrated that the expression of ZAG in patients with cachexia was obviously up-regulated, and it was more remarkable in tumor than in fat tissue.
Conclusion Similar with prostatic and mammary cancer, the expression of ZAG elevated in gastrointestinal cancer patients, and had a further enhancement in patients with cachexia. ZAG expression showed significant relevance with gastrointestinal cancer and cachexia. The content of ZAG between body fluids and tissues was interrelated. The content of ZAG in tumor had a stronger correlation with body fluids than fat tissue suggesting that tumor tissue may be the principle source of ZAG in gastrointestinal cancer patients.
方法：选取复旦大学附属中山医院普外科2009年4月～10月的住院患者,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。要求恶性肿瘤病例为首次诊断的原发性胃肠癌,术前未经治疗,术后经病理确诊。恶病质组的入组标准为患者体重在3月内下降5%以上,或在6月内下降10%以上。收集患者的血清、尿液、腹壁皮下脂肪组织及肿瘤组织四种标本,采用ELISA竞争法定量测定这四种标本中ZAG的含量,采用Western Blot法检测脂肪及肿瘤组织中ZAG的表达情况。所有数据利用SPSS15.0软件进行分析。
结果：本实验入选120名病例,包括男性67名,女性53名,年龄在31～86岁,民族均为汉族。恶性肿瘤病例包括45例胃癌、22例结肠癌以及13例直肠癌,病理均为腺癌。良性对照组包括14例腹外疝、22例胆囊结石、3例胆囊息肉以及1例脾囊肿。三组病例间的性别比例以及年龄无统计学差异。
胃肠癌患者(包括恶病质与非恶病质)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27.1μ/ml与26.1μg／ml,两者差异显著(P<0.001)。恶病质组患者血清、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,但差异无显著性(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(1-=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。
免疫印迹显示,胃肠癌患者两种组织中ZAG的表达均显著高于对照组。恶病质患者脂肪组织中ZAG的表达稍高于非恶病质患者,肿瘤组织中ZAG的表达明显高于非恶病质患者,说明恶病质状态下患者体内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：与前列腺癌、乳腺癌类似,ZAG在胃肠癌患者体内的表达显著升高,在伴有恶病质的患者体内,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,胃肠癌患者体内ZAG的主要来源可能是肿瘤组织本身。
Objective To study the expression of ZAG in patients with or without gastrointestinal cancer and those with or without cachexia. To analyze the relationship between ZAG and gastrointestinal cancer cachexia. To analyze the correlation of ZAG in different tissues and body fluids, and to infer the principle source of ZAG.
Methods From April to October 2009,120 inpatients in the general surgery department of Zhongshan Hospital Affiliated to Fudan University were selected and divided into three groups, including cancer cachexia group(n=40), non-cachexia group(n=40) and control group(n=40).Patients with gastrointestinal cancer were diagnosed for the first time not receiving any preoperative treatments, and confirmed by pathological examination after operations.Patients with cachexia should have lost 5% of their weight in three months, or 10% in six months at least. Four samples, including serum, urine, abdominal subcutaneous fat tissue and tumor tissue, were collected. The contents of ZAG in these samples were quantitatively detected by ELISA respectively. The expressions of ZAG in fat and tumor tissues were detected by Western Blot. SPSS 15.0 was used for statistic analysis.
Results There were 67 males and 53 females in the 120 patients who were between the age of 31 and 86, and all of them belong to Han nationality. All cancer cases were pathological diagnosed as adenocarcinoma, including 45 gastric carcinoma,22 colon carcinoma and 13 rectal carcinoma. The control cases were 14 abdominal external hernia patients,22 cholecystolithiasis patients,3 cholecystic polips patients, and 1 splenic cyst patient aswell.The sex proportion and ages in three groups had no statistic differences.
The average content of ZAG in serum and urine of patients with gastrointestinal cancer were 152.2μg/ml and 158.3μg/ml, significantly higher than those in benign diseases, which were 27.1μg/ml and 26.1μg/ml,respectively (P<0.001).The patients with cachexia had higher levels of ZAG in serum, urine and tumor tissue than those without, with the P value 0.010,0.022 and 0.005 respectively, while in fat tissue there was no significant difference (P=0.060).
The content of ZAG in tumor tissue had a strong correlation with serum and urine with correlation coefficients of 0.735 and 0.676 respectively, while in fat tissue the correlation coefficient were 0.457 and 0.534 respectively. It was thus clear that the content of ZAG in tissues had a positive relationship with body fluids, and it was much stronger in tumor tissue.
Western Blot showed that the expression of ZAG in gastrointestinal cancer patients was markedly increased compare to those in control group both in tumor and fat tissue.The expression of ZAG in patients with cachexia was slightly higher than those without cachexia in fat tissue, while in tumor tissue the difference was much more evident. It illustrated that the expression of ZAG in patients with cachexia was obviously up-regulated, and it was more remarkable in tumor than in fat tissue.
Conclusion Similar with prostatic and mammary cancer, the expression of ZAG elevated in gastrointestinal cancer patients, and had a further enhancement in patients with cachexia. ZAG expression showed significant relevance with gastrointestinal cancer and cachexia. The content of ZAG between body fluids and tissues was interrelated. The content of ZAG in tumor had a stronger correlation with body fluids than fat tissue suggesting that tumor tissue may be the principle source of ZAG in gastrointestinal cancer patients.
引文
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[4]Zuijdgeest-van Leeuwen SD,van den Berg JW, Wattimena JL, et al.Lipolysis and lipid oxidation in weight-losing cancer patients and healthy subjects[J]. Metabolism,2000,49(7):931-6.
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[5]Fouladiun M, Korner U, Bosaeus I,et al.Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care-correlations with food intake, metabolism, exercise capacity, and hormones[J].Cancer,2005,103(10):2189-98.
[6]Slaviero KA, Read JA, Clarke SJ, et al.Baseline nutritional assessment in advanced cancer patients receiving palliative chemotherapy[J].Nutr Cancer,2003, 46(2):148-57.
[7]Trayhurn P, Wood IS.Adipokines:inflammation and the pleiotropic role of white adipose tissue[J].Br J Nutr,2004,92(3):347-55.
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[14]Agustsson T, Ryden M, Hoffstedt J, et al.Mechanism of increased lipolisis in cancer cachexia[J].Cancer Research,2007,67(11):5531-7.
[15]Burgi W, Schmid K. Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma[J].J Biol Chem,1961,236:1066-74.
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