在恶性肿瘤患者中检测蛋白质Z的临床意义

Clinical Significance of Protein Z Detection in Patients with Malignant Tumors

背景与目的:恶性肿瘤患者常存在血液高凝状态,其高凝状态与肿瘤转移的关系越来越受到人们的重视。蛋白质Z(proteinZ,PZ)是一种新发现的抗凝因子,是由肝脏合成的维生素K依赖的血浆蛋白,其结构与维生素K依赖性凝血因子FⅦ、FⅨ、FⅩ及蛋白质C分子十分相似,但其生理功能及临床意义尚不十分明确。临床研究发现PZ水平变化与出、凝血异常导致的疾病危险程度相关。但对实体肿瘤患者PZ水平变化报道很少。本研究重点在探讨恶性肿瘤患者PZ与凝血因子FⅦ∶C、FⅨ∶C、FⅩ∶C、FⅩ∶Ag水平变化的关系及其临床意义。方法:对80例恶性肿瘤患者血浆PZ、FⅦ∶C、FⅨ∶C、FⅩ∶C、FⅩ∶Ag进行测定分析,并作相关性分析;以80名健康人的检测结果作为对照。结果:肿瘤患者的PZ值(1210.89±251.13)滋g/L明显低于健康对照组(2378.83±429.51)滋g/L(P<0.01),但恶性肿瘤组的FⅦ∶C、FⅩ∶C、FⅩ∶Ag水平明显较对照组升高,两组分别为(162.42±36.57)%、(120.27±33.96)%、(133.66±35.51)%和(114.78±28.96)%、(79.23±19.46)%、(93.00±17.73)%(P<0.01),肿瘤患者FⅨ∶C水平(119.86±56.39)%与健康对照者(109.21±36.46)%之间的差异无显著性(P>0.05)。相关性分析发现恶性肿瘤组及对照组中的PZ水平与FⅦ∶C、FⅩ∶C、FⅩ∶Ag水平之间均存在明显负相关(P<0.01),而PZ与FⅨ∶C无显著性相关(P>0.05)。分析肿瘤病程与上述凝血因子的关系发现,Ⅲ～Ⅳ期患者(局部晚期和晚期)PZ水平较Ⅱ期患者降低更明显,分别为(998.32±117.72)ng/ml与(1326.29±245.7)ng/ml(P<0.01);而其FⅦ∶C、FⅩ∶C、FⅩ∶Ag水平比Ⅱ期患者更高[(206.76±28.63)%、(162.53±32.92)%、(168.03±25.97)%vs.(136.09±26.80)%、(101.89±23.44)%、(105.41±13.86)%,P<0.01]。结论:PZ水平在恶性肿瘤患者中明显降低,PZ与FⅦ∶C、FⅩ∶C、FⅩ∶Ag存在明显负相关;PZ水平随着肿瘤病程进展而下降更明显,可能是恶性肿瘤预后不良因素之一。

BACKGROUND ＆ OBJECTIVE. The blood of the patients with malignant tumors is in hypercoagulable state; its correlation to tumor migration evokes more and more attentions. Protein Z （PZ）, a newly found anti-coagulation factor, is a vitamin K-dependent plasma protein which is synthesized by the liver. Its structure is very similar to the vitamin K-dependent coagulation factors, such as FⅦ, FⅨ, FⅩ, and protein C, but its physiologic function and clinical significance are unclear. The alteration of PZ level correlates with the increased risk of coagulating abnormality-caused diseases, but its alteration in solid tumors is seldom reported. This study was to explore clinical significance of PZ and the correlation of PZ level to FⅦ：C; FⅨ：C and FⅩ：C levels in malignant tumors. METHODS： Plasma levels of PZ, FⅦ：C, FⅨ：C, FⅩ ：C, and FⅩ：Ag of 80 patients with malignant tumors （MT group） and 80 healthy donors （control group） were detected; their correlations were analyzed. RESULTS： The level of PZ was significantly lower in MT group than in control group [（1 210.89±251.13） ng/ml vs. （2 378.83±429.51） ng/ml, P〈0.01], but the levels of FⅦ：C, FⅩ：C, and FⅩ：Ag were significantly higher in MT group than in control group [ （162.42±36.57）% vs. （114.78±28.96）%, （120.27±33.96）% vs. （79.23±19.46）%, and （133.66± 35.51）% vs. （93.0±17.73）%, P〈0.01]. The levels of FⅨ：C were （119.86±56.38）% in MT group, and （109.21±36.46）% in control group （P〉0.05）. The level of PZ was negatively correlated with the levels of FⅦ：C; FⅩ ：C, and FⅩ ：Ag （P〈0.01）, but had no correlation with the level of FⅨ：C （P〉0.05）. The level of PZ was significantly lower in stage Ⅲ -Ⅳ （locally advanced stage-advanced stage） patients than in stage Ⅱ patients [ （998.32±117.72） ng/ml vs. （1 326.69±245.70） ng/ml, P〈0.01 ], but the levels of FⅦ：C, FⅩ：C, and FⅩ：Ag were significantly higher in stage Ⅲ-Ⅳ patients than in stage Ⅱ patients [ （206.76± 28.63）% vs. （136.09 ±26.80）%, （162.53 ±32.92）% vs. （101.89±23.44）%, （168.03±25.97）% vs. （105.41%±13.86）%, P〈0.01]. CONCLUSIONS： PZ level is obviously decreased in the patients with malignant tumors, and negatively correlated with FⅦ：C, FⅩ：C, and FⅩ：Ag. PZ level descends along with the progression of malignant tumors, and maybe a poor prognostic factor of malignant tumors.