Many studies have explored the role of slug in the prognosis and clinicopathological parameters of breast cancer, but the results were inconsistent. Therefore, we determined the relationship between high slug expression in breast cancer and prognosis and clinicopathological parameters by this meta-analysis. Our meta-analysis shows that high expression of slug in breast cancer is associated with worse OS（pooled HR= 2.21;95%CI=1.47-3.33;p＜0.001）and DFS(pooled HR=2.03; 95%CI = 1.26 -3.28;P=0.004)，To further investigate the role of slug in breast cancer，We analyzed the relationship between slug and clinicopathological parameters of breast cancer，the results show that high expression of slug in breast cancer have higher TNM stage(I-II/III-IV; pooled OR=0.42;95%CI=0.25-0.70;P=
0.001),more prone to axillary lymph node metastasis(N+/N0; pooled OR=2.16; 95%CI = 1.31-3.56;P=0.003) and more severe ER deficiency (positive / negative; pooled OR =0.62; 95% CI= 0.41 -0.93;P=0.021)，and it is worth noting that the relationship between high expression of slug and ER status has been demonstrated in many studies[28, 29].
Slug is associated with prognosis in a variety of cancer cells. Liu et al. and Song et al.found that slug is expressed more in lung cancer cells than in normal lung tissue, and high expression of slug in lung tumor cells is associated with poor survival and more aggressive clinicopathological parameters. Chang et al.  and Gu et al. found that slug is highly correlated with the invasiveness and drug resistance of ovarian cancer cells. Toiyamo et al.  found that slug expression was significantly increased in colorectal cancer with high T stage, liver metastasis and lymph node metastasis, it may be a potential prognostic marker for colorectal cancer. The relationship between slug and solid tumor was analyzed in a previous study  , interestingly ,it found that slug is associated with a poor prognosis in lung cancer、head and neck carcinoma、urinary cancer、 gastrointestinal tract carcinoma, but not in breast cancer.
Metastasis of tumor cells and the drug resistance to anti-tumor therapy are the main causes of poor prognosis in cancer patients. Pan et al.and Shao et al.demonstrated that slug is an important factor in promoting the metastasis of breast cancer cells and may be an important marker of metastasis potential. Slug, as a member of EMT, was initially recognized for its involvement in the EMT project,. During the progression of breast cancer, cells and cell adhesion are lost in the EMT process, resulting in migration and invasion [38, 39].There are many molecular mechanisms that slug promotes the metastasis of cancer underlying EMT. Liu et al found that slug represses the expression of miR-200b and miR-1,and the inhibition of miR-200b and miR-1 promote EMT and tumor cell invasiveness. Fazilaty et alfound that slug can induce TNC and Postn by signal cascade, thus promoting the invasiveness of tumor cells. What’s more, Lamouille et al. found that the high expression of slug decrease the expression of epithelial genes and activate the expression of mesenchymal genes, which promotes the metastasis of the tumor cells.
High expression of slug can lead to multiple drug resistance [12, 13]. Slug has recently been found to play an important role in tamoxifen resistance of breast cancer[29, 43]. The expression of slug prevented the killing effect of tamoxifen on ER(+) breast cancer cells. Slug has been shown to induce endocrine therapy resistance in breast cancer cells by altering the cell survival signaling pathways, leading to worse DFS.Musgrove et Al. found that the loss of ER expression due to high expression of slug is the main cause of drug resistance in tamoxifen. Some studies suggested that slug induces tamoxifen resistance by increasing EGFR expression and Erk phosphorylation. what’s worse, Li et al.  found that slug can induce chemotherapy resistance in cancer cells via PI3K/Akt/GSK3b pathway. These studies confirm that slug leads to poor prognosis in breast cancer, consistent with our Meta-analysis results.
Our meta-analysis shows that slug is a key biomarker for predicting prognosis in breast cancer patients, which is the main finding of this study. No heterogeneity or publication bias was found in this meta-analysis, and sensitivity analysis suggested that our results were reliable. There were limitations in our meta-analysis. First, there was no uniform scoring criterion to define the cut-off of the high expression of slug. Second, there were differences in the type and dilution of immunohistochemical antibodies. Third, HR reliability of some prognostic parameters obtained from Kaplan-Meier curve was poor. Fourth , even though we screened through 1,186 articles, we ended up with only eight available studies, and only one of them from a non-Asian population, so more studies were need in non-Asians in the future .