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巨噬细胞集落刺激因子、基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1作为宫颈癌患者肿瘤标志物的血浆水平及诊断效用

Plasma levels and diagnostic utility of macrophage-colony stimulating factor, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 as tumor markers in cervical cancer patients.

作者信息

Zajkowska Monika, Zbucka-Krętowska Monika, Sidorkiewicz Iwona, Lubowicka Emilia, Gacuta Ewa, Szmitkowski Maciej, Chrostek Lech, Ławicki Sławomir

机构信息

1 Department of Biochemical Diagnostics, Medical University of Białystok, Białystok, Poland.

2 Department of Reproduction and Gynecological Endocrinology, Medical University of Białystok, Białystok, Poland.

出版信息

Tumour Biol. 2018 Jul;40(7):1010428318790363. doi: 10.1177/1010428318790363.

Abstract

Macrophage-colony stimulating factor, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play an important role in malignant processes. The aim of this study was to investigate the diagnostic power of those parameters (serological biomarkers) in comparison to cancer antigen 125 and squamous cell carcinoma antigen in cervical cancer patients and in relation to the control groups. The study included 100 cervical cancer patients, 50 patients with cervical ectropion and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, cancer antigen 125, and squamous cell carcinoma antigen by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases p < 0.05). In stage I of cancer only medial supraclavicular fossa and tissue inhibitor of metalloproteinase-1, in stage II all the tested parameters and cancer antigen 125, and in stage III + IV macrophage-colony stimulating factor, matrix metalloproteinase-9, and cancer antigen 125 showed statistical significance when compared to the healthy volunteers group. Macrophage-colony stimulating factor showed the highest value of sensitivity from all tested parameters (I: 56.25%, II: 72.73%, III + IV: 77.14% and 69% in total cervical cancer group). The highest specificity was obtained by matrix metalloproteinase-9 (94%). Positive predictive values were highest also for matrix metalloproteinase-9 (I: 82.35%, II: 84.21%, III + IV: 88% and 94.55% in total cervical cancer group), negative predictive values for macrophage-colony stimulating factor (I: 75.44%, II: 82.69%, III + IV: 87.5% and 58.11% in total cervical cancer group) and tumor markers. In the total cervical cancer group, all tested parameters showed statistically significant areas under receiver operating characteristic curve, but maximum range was obtained for the combination macrophage-colony stimulating factor + squamous cell carcinoma antigen (0.8723). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and areas under receiver operating characteristic curve values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of cervical cancer in the future.

摘要

巨噬细胞集落刺激因子、基质金属蛋白酶-9和金属蛋白酶组织抑制剂-1可能在恶性肿瘤进程中发挥重要作用。本研究旨在探讨这些参数(血清生物标志物)相较于癌抗原125和鳞状细胞癌抗原在宫颈癌患者中的诊断效能,并与对照组进行比较。该研究纳入了100例宫颈癌患者、50例宫颈外翻患者和50例健康女性。通过酶联免疫吸附测定法测定所检测参数的血浆水平,通过化学发光微粒子免疫测定法测定癌抗原125和鳞状细胞癌抗原。全部癌症组中所有参数的血浆水平均具有统计学意义(所有情况p < 0.05)。在癌症I期,仅锁骨上窝中部和金属蛋白酶组织抑制剂-1具有统计学意义;在II期,所有检测参数和癌抗原125具有统计学意义;在III + IV期,与健康志愿者组相比,巨噬细胞集落刺激因子、基质金属蛋白酶-9和癌抗原125具有统计学意义。在所有检测参数中,巨噬细胞集落刺激因子的敏感性最高(I期:56.25%,II期:72.73%,III + IV期:77.14%,在全部宫颈癌组中为69%)。基质金属蛋白酶-9的特异性最高(94%)。基质金属蛋白酶-9的阳性预测值也最高(I期:82.35%,II期:84.21%,III + IV期:88%,在全部宫颈癌组中为94.55%),巨噬细胞集落刺激因子的阴性预测值(I期:75.44%,II期:82.69%,III + IV期:87.5%,在全部宫颈癌组中为58.11%)以及肿瘤标志物的阴性预测值。在全部宫颈癌组中,所有检测参数在受试者工作特征曲线下均显示出统计学意义的面积,但巨噬细胞集落刺激因子 + 鳞状细胞癌抗原组合的面积最大(0.8723)。对检测参数和肿瘤标志物的联合分析导致敏感性增加以及受试者工作特征曲线下面积值增加,这为未来开发可用于宫颈癌诊断的新型生物标志物组合带来了希望。

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