Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, China.
Sci Rep. 2019 Aug 12;9(1):11677. doi: 10.1038/s41598-019-47871-5.
Ovarian cancer has a high death rate and is often not detected until late stages. While some studies found high expressions of MMPs correlated with cancer invasion, metastasis, and poor prognosis, however, several other studies indicated MMPs might inhibit cancer rather than promote cancer in certain situations. Thus, the role of different MMPs in different cancer types needs a systematic re-evaluation. In this study, we used RNA-Seq and corresponding clinical data downloaded from TCGA and analyzed the correlations between MMP expressions and the clinicopathologic characteristics and outcome in ovarian serous cystadenocarcinoma (OSC) patients. Among the MMPs investigated, MMP-3 was significantly increased in high-grade and high-stage tumors compared with low-grade and low-stage ones. Using univariate analysis and multivariate Cox model, high expressions of MMP-19 and -20 were found to associate with poor overall survival independent of clinicopathologic characteristics. Moreover, using in vitro studies, we found ovarian cancer cell lines with higher MMP-19 and -20 protein expressing levels were associated with anti-cancer drugs resistance, while knockdown of MMP-19 or -20 increased ovarian cancer cell sensitivities to several clinical using chemotherapy agents. Finally, knockdown of MMP-19 or -20 also decreased the invasion abilities of several ovarian cancer cell lines. These in vitro studies provided potential mechanisms of high MMP-19 and -20 expressions in the poor prognosis of ovarian cancer.
卵巢癌死亡率高，通常在晚期才被发现。虽然一些研究发现 MMPs 的高表达与癌症的侵袭、转移和不良预后相关，但也有其他一些研究表明，在某些情况下，MMPs 可能抑制癌症而不是促进癌症。因此，不同 MMPs 在不同癌症类型中的作用需要进行系统的重新评估。在这项研究中，我们使用 RNA-Seq 技术和从 TCGA 下载的相应临床数据，分析了 MMP 表达与卵巢浆液性囊腺癌（OSC）患者的临床病理特征和预后之间的相关性。在所研究的 MMP 中，MMP-3 在高级别和高分期肿瘤中的表达明显高于低级别和低分期肿瘤。通过单因素分析和多因素 Cox 模型分析，发现 MMP-19 和 MMP-20 的高表达与临床病理特征无关，与总生存期不良独立相关。此外，通过体外研究，我们发现 MMP-19 和 MMP-20 蛋白表达水平较高的卵巢癌细胞系与抗癌药物耐药性相关，而 MMP-19 或 MMP-20 的敲低则增加了卵巢癌细胞对几种临床化疗药物的敏感性。最后，MMP-19 或 MMP-20 的敲低也降低了几种卵巢癌细胞系的侵袭能力。这些体外研究提供了 MMP-19 和 MMP-20 高表达导致卵巢癌预后不良的潜在机制。
