Biochemistry Research Division, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.
Int J Biol Markers. 2011 Jan-Mar;26(1):27-36. doi: 10.5301/jbm.2011.6359.
Oral cancer is a major health hazard worldwide with increasing incidence and mortality. Cervical lymph node metastasis is a major determinant of outcome in oral cancer. The matrix metalloproteinase (MMP) system is critically involved in invasion and metastasis. Assessment of MMPs and tissue inhibitors of MMPs (TIMPs) in certain combinations might have better clinical efficacy given their potential role in the metastatic process.
Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 50 controls and 75 oral cancer patients (nonmetastatic, n=54; metastatic, n=21) were evaluated to assess their investigative value and role in predicting the behavior of this malignancy.
The plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were quantified by ELISA. The best 2- and 3-marker combinations were calculated using the statistical software mROC. The diagnostic values for all the biomolecules as single markers and their combinations were estimated using the measures of diagnostic accuracy, i.e. the area under the ROC curve and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 95% limits of sensitivity and specificity, respectively.
MMP-9, TIMP-1 and TIMP-2 were significantly elevated (p=0.000, p=0.013 and p=0.005, respectively) in oral cancer patients. MMP-9 emerged as the best single statistically significant marker in plasma for oral cancer detection. It showed an increase in diagnostic performance when tested in combination with MMP-2 and TIMP-2. The median plasma MMP-9 levels were elevated in both the metastatic and nonmetastatic groups compared with controls (p<0.004 and p<0.007, respectively).
The results indicated that plasma MMP and TIMP levels in relevant combinations may facilitate clinical decisionmaking for improved management of oral cancer patients and may provide important data for selecting patients for treatment with drugs that interfere with MMP and TIMP activities.
口腔癌是全球范围内的主要健康危害，其发病率和死亡率呈上升趋势。颈部淋巴结转移是口腔癌预后的主要决定因素。基质金属蛋白酶（MMP）系统在侵袭和转移中起着关键作用。评估 MMP 和基质金属蛋白酶组织抑制剂（TIMP）的某些组合可能具有更好的临床疗效，因为它们在转移过程中具有潜在作用。
评估 50 例对照者和 75 例口腔癌患者（无转移，n=54；转移，n=21）的血浆中 MMP-2、MMP-9、TIMP-1 和 TIMP-2 的浓度，以评估其在预测这种恶性肿瘤行为方面的价值和作用。
采用 ELISA 法检测 MMP-2、MMP-9、TIMP-1 和 TIMP-2 的血浆浓度。使用统计软件 mROC 计算最佳的 2 标志物和 3 标志物组合。使用诊断准确性的度量标准，即 ROC 曲线下面积以及在最高诊断准确性和 95%敏感性和特异性限制内的截断值处的敏感性和特异性，评估所有生物标志物作为单一标志物及其组合的诊断价值。
口腔癌患者的 MMP-9、TIMP-1 和 TIMP-2 显著升高（p=0.000、p=0.013 和 p=0.005）。MMP-9 是血浆中检测口腔癌的最佳单标志物，与 MMP-2 和 TIMP-2 联合检测时，诊断性能提高。与对照组相比，转移性和非转移性组的中位血浆 MMP-9 水平均升高（p<0.004 和 p<0.007）。
结果表明，相关组合的血浆 MMP 和 TIMP 水平可能有助于临床决策，改善口腔癌患者的管理，并为选择接受干扰 MMP 和 TIMP 活性的药物治疗的患者提供重要数据。
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