Incorvaia Lorena, Badalamenti Giuseppe, Rini Giovambattista, Arcara Carlo, Fricano Salvatore, Sferrazza Carmela, Di Trapani Danilo, Gebbia Nicola, Leto Gaetano
Section of Clinical Oncology, Policlinico Unversitario "Paolo Giaccone", 90127 Palermo, Italy.
Anticancer Res. 2007 May-Jun;27(3B):1519-25.
The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis.
MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA).
Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy.
Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better defined.
研究了患有（M1）或未患有（M0）骨转移的乳腺癌（BC）或前列腺癌（PC）患者中激活素A以及基质金属蛋白酶-2（MMP-2）和-9（MMP-9）循环水平的临床意义。
通过酶免疫测定法测量了79例癌症患者和57名作为对照组的健康献血者（HS）的MMP-2、MMP-9和激活素A血浓度。通过受试者工作特征曲线（ROC）评估这些分子区分M0和M1患者的诊断准确性，并与肿瘤标志物CA15.3或前列腺特异性抗原（PSA）的诊断准确性进行比较。
与性别匹配的HS相比，BC和PC患者中的激活素A和MMP-2显著升高，而MMP-9水平仅在PC患者中升高得更多。有趣的是，在PC患者中，激活素A水平显著高于BC患者中测得的水平。在后者组中，与M0患者相比，M1患者中的激活素A和CA15.3升高，但MMP-2或MMP-9未升高。此外，还突出显示了激活素A浓度与骨转移数量和肿瘤分级之间、MMP-9与肿瘤分级之间以及MMP-2与CA15.3之间存在显著关系。ROC曲线分析显示，激活素A和CA15.3在区分M0和M1患者方面具有良好的诊断准确性，但MMP-2和MMP-9的准确性较差。然而，CA15.3在这方面保持了最佳诊断准确性。在PC组中，与M0患者相比，M1患者中仅激活素A和PSA水平显著升高。MMP-9也观察到类似趋势，尽管无统计学意义。有趣的是，观察到PSA与激活素A和MMP-9之间以及激活素A与Gleason评分和骨转移数量之间存在显著相关性。ROC曲线分析显示，激活素A、MMP-9和PSA在检测M1患者方面具有良好的诊断准确性，而MMP-2的诊断准确性较差。然而，PSA显示出最高的诊断准确性。
激活素A、MMP-2和MMP-9可被视为转移性骨病治疗中可能的治疗靶点。然而，它们作为骨转移附加标志物的有用性仍有待更好地确定。
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