Department of Surgery, Children's Hospital Boston, Boston, MA, USA.
Gynecol Oncol. 2011 Nov;123(2):295-300. doi: 10.1016/j.ygyno.2011.07.034. Epub 2011 Sep 1.
To determine whether urinary matrix metalloproteinases (MMPs) predict the presence of ovarian cancer in patients with CA125 levels below the normal threshold of 35U/mL, a critical group of patients for whom no ovarian cancer biomarker is currently available. To determine whether these noninvasive biomarkers provide clinically useful information in the general ovarian cancer patient population as well.
ELISA analyses and substrate gel electrophoresis detected the levels and activity of urinary MMP-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex, and MMP-9 dimer in all ovarian cancer patients (n=97), those with CA125 <35U/mL (n=26) and controls (n=81).
In patients with CA125 <35U/mL, receiver-operating characteristic (ROC) area under curve (AUC) analysis demonstrated that either urinary MMP-2 or MMP-9 or NGAL significantly discriminated between controls and ovarian cancer patients with normal CA125. Multivariate logistic regression revealed that the combination of urinary MMP-2 and MMP-9 provided the best diagnostic accuracy when multiplexed. When further multiplexed with age, the diagnostic accuracy of these biomarkers increased to a significant AUC of 0.820. These findings were consistent among the general ovarian cancer population studied as well, where the combination of urinary MMP-2 and MMP-9 multiplexed with age resulted in a highly significant AUC of 0.881. Pearson chi-square analysis revealed that higher urinary levels of either MMP-2 or MMP-9 were strongly associated with the increasing percentage of women with ovarian cancer independent of CA125 levels.
This study demonstrates the potential utility of urinary MMP-2 and MMP-9 to differentiate between ovarian cancer patients with normal CA125 levels and controls and suggests that urinary MMP-2 and MMP-9 may be a clinically useful aid in the diagnosis of advanced or recurrent ovarian cancer.
确定尿基质金属蛋白酶 (MMPs) 是否可预测 CA125 水平低于正常阈值 35U/mL 的卵巢癌患者的存在，这是一组尚无卵巢癌生物标志物的关键患者群体。并确定这些非侵入性生物标志物是否也可为一般卵巢癌患者群体提供有临床价值的信息。
采用 ELISA 分析和底物凝胶电泳检测所有卵巢癌患者（n=97）、CA125<35U/mL 患者（n=26）和对照组（n=81）的尿 MMP-2、MMP-9、MMP-9/中性粒细胞明胶酶相关脂质运载蛋白（NGAL）复合物和 MMP-9 二聚体的水平和活性。
在 CA125<35U/mL 的患者中，受试者工作特征（ROC）曲线下面积（AUC）分析表明，尿 MMP-2 或 MMP-9 或 NGAL 均能显著区分正常 CA125 的对照组和卵巢癌患者。多变量逻辑回归显示，尿 MMP-2 和 MMP-9 的组合在多重检测时提供了最佳的诊断准确性。当进一步与年龄多重检测时，这些生物标志物的诊断准确性提高到具有显著意义的 AUC 为 0.820。这些发现也在研究的一般卵巢癌患者群体中一致，其中尿 MMP-2 和 MMP-9 与年龄多重检测时的 AUC 高达 0.881，具有高度显著意义。Pearson 卡方分析表明，尿 MMP-2 或 MMP-9 的水平升高与卵巢癌患者的百分比呈正相关，与 CA125 水平无关。
本研究表明尿 MMP-2 和 MMP-9 具有区分正常 CA125 水平的卵巢癌患者和对照组的潜力，并表明尿 MMP-2 和 MMP-9 可能是诊断晚期或复发性卵巢癌的一种有临床价值的辅助手段。
