胃癌患者外周血半乳糖凝集素-3及基质金属蛋白酶2、9的变化

E. Korotkova, E. S. Gershtein, E. V. Samoilova, I. O. Goryacheva, Aram P. Petrosyan, N. Zybina, O. Yanushevich, I. Stilidi, N. Kushlinskii
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引用次数: 0

摘要

背景:胃癌(GC)的高发病率,其病程侵袭性,肿瘤播散迅速,对化疗敏感性低,缺乏可靠的实验室诊断标准,迫切需要寻找与肿瘤关键生物学特性相关的最具信息量的标志物。目的:比较分析GC患者与健康供者外周血半乳糖凝集素-3、基质金属蛋白酶(MMP)-2、MMP-9水平,探讨这些指标与胃癌临床形态学特征、总生存期和无复发生存期预后的关系。材料和方法:60例(60例)未接受过初级治疗的胃癌患者(男38例,女22例),年龄29 ~ 81岁,90例与其年龄和性别相符的健康供体。采用标准的直接酶免疫测定试剂盒“Human MMP-2 (total)”、“Human MMP-9 (total)”、“Human Galectin-3”(RD Systems, USA)测定EDTA血浆中半乳糖凝集素-3、血清中MMP-2和MMP-9。结果:胃癌患者血浆半乳糖凝集素-3浓度显著高于健康对照组(中位数分别为12.9和10.6 ng/ml;p 0.0001)。GC组与对照组血清MMP-9水平无差异,对照组血清MMP-2水平显著高于GC组(p = 0.039)。GC患者血液中半乳糖凝集素-3、MMP-2和MMP-9水平之间没有相关性。与GC患者相比,对照组血浆半乳糖凝集素-3与年龄呈正相关(rs = 0.51, p 0.005)。血液中的生物标志物水平与GC的临床和形态学特征之间没有关联,除了MMP-9在Т4а侵袭深度比先前的Т2水平更高。血浆半乳糖凝集素-3水平差异显著,截止水平为12.9 ng/ml:低半乳糖凝集素-3患者的5年总生存率优于高半乳糖凝集素-3患者(分别为50%和43%);然而,差异无统计学意义(0.01)。血清MMP-2水平低(212 ng/ml)的GC患者的总生存率和无复发生存率均较高:该组5年总生存率为60%,而MMP-2水平高的患者为23% (p = 0.018)。无复发生存率差异无统计学意义。血清MMP-9水平对胃癌患者的生存无显著影响。结论:本研究获得的关于半乳糖凝集素-3、MMP-2、MMP-9在胃癌中的临床作用的模糊数据表明,有必要进一步研究它们在诊断和治疗结果预后方面的可能用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Galectin-3 and matrix metalloproteinases 2 and 9 in peripheral blood of gastric cancer patients
Background: High incidence of gastric cancer (GC), its aggressive clinical course, rapid tumor dissemination, low sensitivity to chemotherapy and lack of reliable laboratory diagnostic criteria urgently require a search for the most informative markers associated with key biologic properties of the tumors. Aim: Comparative analysis of galectin-3, matrix metalloproteinase (MMP)-2, and MMP-9 levels in peripheral blood of GC patients and healthy donors, assessment of association of these markers with clinical morphological characteristics of the disease, and prognosis of overall and relapse-free survival. Materials and methods: Sixty (60) primary treatment-nave GC patients (38 men, 22 women) aged 29 to 81 years and 90 healthy donors compatible with their age and sex were included into the study. Galectin-3 was measured in EDTA plasma, MMP-2 and MMP-9 in serum with standard direct enzyme immunoassay kits "Human MMP-2 (total)", "Human MMP-9 (total)", "Human Galectin-3" (RD Systems, USA). Results: Plasma galectin-3 concentration in the GC patients was significantly higher than in the healthy controls (median 12.9 and 10.6 ng/ml, respectively; p 0.0001). No difference in serum MMP-9 levels between GC patients and control subjects were found, while MMP-2 level in the control group was significantly higher, than in the GC patients (p = 0.039). No association between galectin-3, MMP-2, and MMP-9 blood levels in the GC patients could be identified. In contrast to GC patients, there was a positive correlation of plasma galectin-3 with age in the control group (rs = 0.51, p 0.005). No associations between the biomarkers levels in blood and clinical and morphological characteristics of GC were established, except MMP-9 being higher at Т4а invasion depth as compared to the earlier Т2 level. Marked differences in the overall survival depending on plasma galectin-3 levels were found, with the cut-off level of 12.9 ng/ml: the 5-year overall survival in the patients with low galectin-3 was better, than in those with its higher level (50 and 43%, respectively; however, the difference was non-significant, р 0.1). Both overall and relapse-free survival of the GC patients was higher in those with low ( 212 ng/ml) serum MMP-2: the 5-year overall survival in this group comprised 60% versus 23% in the patients with higher MMP-2 (p = 0.018). The difference in relapse-free survival was non-significant. Serum MMP-9 levels had no significant impact on the survival of GC patients. Conclusion: The ambiguous data on the clinical role of galectin-3, MMP-2, MMP-9 in GC obtained in this study indicate the necessity of further investigation of their possible utility for the diagnostics and prognosis of treatment results.
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