Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S375-84. doi: 10.1245/s10434-011-1836-7. Epub 2011 Jun 17.
The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.
MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).
Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.
MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.
细胞外基质金属蛋白酶 MMP-9 和 MMP-2 对于肿瘤的侵袭潜能至关重要。然而，目前尚不清楚这两种酶在肿瘤侵袭和进展中哪种起主要作用。在本研究中，我们比较了 MMP-9 和 MMP-2 过表达对预测 HCC 患者手术后肿瘤复发和生存的临床疗效。
通过定量 RT-PCR 和免疫荧光检测 HCC 细胞系和体外 HCC 侵袭模型中的 MMP-9 和 MMP-2 表达。采用免疫组织化学方法检测 HCC 组织微阵列中 MMP-9 和 MMP-2 的表达水平，该微阵列来自接受根治性切除术的 HCC 患者（研究组）。回顾性分析临床病理数据。在 92 例 HCC 患者的独立队列（验证组）中进一步验证了这些结果。
单因素分析表明，MMP-9 高表达与复发时间（TTR，P =.015）和总生存期（OS，P =.024）均相关，而 MMP-2 高表达仅与 TTR 相关（P =.041）。多因素分析证实 MMP-9 表达是 TTR 和 OS 的独立预测因子。MMP-9 和术前血清 AFP 水平的共同指数与 TTR 和 OS 显著相关（P =.036 和 P =.040），但 MMP-2 和 AFP 的共同指数对 TTR 和 OS 均无预后意义（P =.067 和 P =.053）。MMP-9 过表达的预后价值在独立数据集得到验证。
MMP-9 比 MMP-2 更能预测 HCC 患者手术后肿瘤复发和生存。
