1. Academic Validation
  2. Matrix Metalloproteinase Expressions Play Important role in Prediction of Ovarian Cancer Outcome

Matrix Metalloproteinase Expressions Play Important role in Prediction of Ovarian Cancer Outcome

  • Sci Rep. 2019 Aug 12;9(1):11677. doi: 10.1038/s41598-019-47871-5.
Shujie Wang 1 2 Jia Jia 1 2 Dongyan Liu 1 2 Meng Wang 3 Zhen Wang 3 Xueling Li 1 2 Hongzhi Wang 1 2 Yong Rui 2 Zhirong Liu 2 Wei Guo 1 2 Jinfu Nie 4 5 6 Haiming Dai 7 8
Affiliations

Affiliations

  • 1 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.
  • 2 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, China.
  • 3 Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Hefei, China.
  • 4 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. jinfunie@163.com.
  • 5 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, China. jinfunie@163.com.
  • 6 Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Hefei, China. jinfunie@163.com.
  • 7 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. Daih@cmpt.ac.cn.
  • 8 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, China. Daih@cmpt.ac.cn.
Abstract

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.

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