Yu et al. Journal of Experimental & Clinical Cancer Research 2010, 29:119 http://www.jeccr.com/content/29/1/119 Page 8 of 9 independently of E-cadherin expression[38-42]. Then, it strengthens the argument to justify both Slug or Snail or Twist expression and potential downstream targets as E-cadherin expression evaluation. It has already been demonstrated that Slug, Snail or Twist overexpression was associated with poor outcome and shorter survival in patients with solid tumors [31-34]. Our findings support this hypothesis as E-cad- herin and Twist expression were associated with poor survival both in univariate and multivariate analyses of all factors that influenced survival. Franck Bruyere et al.[43]have found that high expres- sion of Snail in superficial bladder tumors significantly predicts tumor recurrence in these patients. But we did not find any relationship between the expression of Snail and tumor recurrence. That we had a different way to evaluate the immunohistochemistry results may be the reasons. The univariate analysis showed that high Snail expres- sion, histologic grading, CIS and E-cadherin(P = 0.005) were statistically significant risk factors. The backward stepwise multivariate analysis showed that high Snail and Slug expression and E-cadherin were statistically significant independent risk factors. One mechanism of the link between Slug, Snail or Twist expression and poor prognosis may be the reducing of E-cadherin expression allowing cancer cells to migrate but it is probably not the only one[38-42]. Moreover, in our study, we noticed that some patients with high-risk superficial bladder tumors that High expressed Slug, Snail or Twist displayed distant metasta- sis within 2 years after initial diagnosis even if a cystect- omy was performed. We also noticed that among patients who benefited from a cystectomy for invasive bladder tumor, 10/18 had lymph node metastasis with a bladder tumor high expressing Slug, Snail or Twist and without E-cadherin expression. These results suggest that although the prognostic value of Slug, Snail or Twist should be confirmed in a larger number of patients, its expression could be a useful marker for selecting patients with a high risk of a poor clinical out- come and for proposing a better therapy to them. The inhibition of Slug, Snail or Twist action through interfering RNA (siRNA)or antisense transfer resulted in tumor metastasis or growth inhibition and increased sensitivity to the cytotoxic agents used in chemotherapy for solid cancers [29,44-46]These results strongly sug- gest the relation between EMT markers induction including Slug, Snail and Twist but also between anti- Slug, Snail or Twist treatment and improvement of bladder cancer chemotherapy. In conclusion, the EMT regulatory proteins Slug and Twist are upregulated in human BT, whereas Snail is downregulated. Such disparate expression levels may contribute to the progression of tumors in BT, and this deserves further investigation. Our results highlighted the potential role of Twist, Snail and Slug as the prog- nostic factor in bladder cancer. They could be a very useful molecular marker of progression in BT. If our findings are validated by additional studies, Slug, Snail and Twist expression could be used as a predictive fac- tor in bladder cancer but also as a novel target for clini- cal therapy. Identifying new molecular markers could also be the first step to accurately define a high risk-of- progression molecular profile in BT. Acknowledgements We take this opportunity to specifically thank the reviewers and editors for their kind instructions that may be helpful for our further studies. Author details 1Department of Urology surgery, the Affiliated Hospital of medical college, QingDao University, QingDao, Shan Dong Province, 266403, China. 2Department of General surgery, the Affiliated Hospital of medical college, QingDao University, QingDao, Shan Dong Province, 266403, China. 3Department of molecular biology, the Affiliated Hospital of medical college, QingDao University, QingDao, Shan Dong Province, 266403, China. Authors’ contributions QC and XS designed the experiments. KJ and XP carried out most of experiments and drafted the manuscript. ZM carried out the western blotting and KJ participated in statistical analysis and and interpretation of data. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 3 July 2010 Accepted: 1 September 2010 Published: 1 September 2010 References 1. 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