原发性肝癌患者血清及癌组织GPDA糖链异质体的研究

目的：研究原发性肝癌（PHC）患者血清，肝癌组织甘氨酰脯氨酸二肽氨基肽酶（GPDA）糖链异质体的变化和对PHC的诊断价值。方法：测定265例HPHC，良性肝病患者及正常对照血清GPDA总活性（TGPDA），利用刀豆素A（ConA)与等量血清孵育法将GPDA分为刀豆素A结合型与非结合型两种异质体。测定非结合型活性，计算结合型活性（总活性减去非结合型活性）；同方法PHC患者肝组织中GPDA总活性和非结合型活性，根据测定的蛋白浓度分别计算两者的比活性。结果：PHC患者血清非结合型活性显著高于慢性肝炎，肝硬化和正常对照组（P均＜0．01）及急性肝炎组（P＜0．05）；各受检组血清结合型活性均显著高于与该组非结合型的活性（P均＜0．01）；PHC患者血清结合型活性与正常人比无 显著差异（P＞0．01）。结论：分别以TGPDA及非结合型作为PHC诊断的指标，两者特异性相近，而敏感性，准确率均高于TGPDA。推测非结合型异常增高可能源于肿瘤组织的膜结合部分的过量合成，并从膜结合部分释放入可溶性部分而致。

STUDY ON THE GLYCOFORMS OF GPDA IN THE SERUM AND LIVER TISSUES IN PATIENTS WITH PHC

Objective:To study the variation of glycoforms of glycylproline depeptidyl aminopeptidase(GPDA) in the sera and liver tissues in patients with primary hepatic carcinoma(PHC).Methods:Serum total GPDA(TGPDA) activities in 91 patients with PHC,23 patients with acute hepatitis(AH),25 patients with chronic hepatitis(CH),37 petients with liver cirrhosis(LC) and 89 healthy persons were measured with the method reported by Cao Xingjian.The glycoforms of serum GPDA was separated by incubating with concanavalin A solution,then detect the activity of ConA-non-reactive fraction(GPDA-N-ConA).The activity of ConA-reactive fraction (GPDA-R-ConA) was obtained by subtracting GPDA-N-ConA from TGPDA.Using the same method we measured TGPDA and GPDA-N-ConA in liver tissues in patients with PHC.Result:Serum GPD-N-ConA activities in patients with PHC were significantly higher than those of CH,LC,Norm(P<0.01) and AH(P<0.05).There was no significant difference between the serum GPDA-R-ConA in patients with PHC and in Norm (P>0.01).The diagnostic sensitivity,specificity and accuracy of serum TGPDA and werum GPDA-N-ConA were 38.5%,90.8%,72.8% and 67.0%,87.4%,80.4% respectively.TGPDA and GPDA-N-ConA activities in the whole cancerous tissues and their soluble parts in patients with PHC were significantly higher than those of the liver tissues adjacent to the tumor.The GPDA-N-ConA activities of membrane-bound GPDA were significantly higher than those of soluble parts (P<0.05).Conclusion:Serum GPDA-N-ConA is a useful marker of PHC and better than TGPDA in the diagnosis of PHC.The increase of serum GPDA is mainly due to the increase of serum GPDA-N-ConA.The increase of GPDA-N-ConA in liver tissues in patients with PHC may due to the hyperproduction of membrane-bound GPDA.