Co-expression of ERCC1 and Snail is a prognostic but not predictive factor of cisplatin-based neoadjuvant chemotherapy for bladder cancer

Kawashima,Atsunari; Takayama,Hitoshi; Kawamura,Norihiko; Doi,Noriteru; Sato,Mototaka; Hatano,Koji; Nagahara,Akira; Uemura,Motohide; Nakai,Yasutomo; Nishimura,Kensaku; Miyoshi,Susumu; Kawano,Kiyoshi; Nishimura,Kazuo; Nonomura,Norio; Tsujimura,Akira

doi:10.3892/ol.2012.689

Co-expression of ERCC1 and Snail is a prognostic but not predictive factor of cisplatin-based neoadjuvant chemotherapy for bladder cancer

Authors:
- Atsunari Kawashima
- Hitoshi Takayama
- Norihiko Kawamura
- Noriteru Doi
- Mototaka Sato
- Koji Hatano
- Akira Nagahara
- Motohide Uemura
- Yasutomo Nakai
- Kensaku Nishimura
- Susumu Miyoshi
- Kiyoshi Kawano
- Kazuo Nishimura
- Norio Nonomura
- Akira Tsujimura
View Affiliations

Affiliations: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan, Department of Urology, Osaka Rosai Hospital, Sakai, Japan, Department of Pathology, Osaka Rosai Hospital, Sakai, Japan, Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
Published online on: April 23, 2012 https://doi.org/10.3892/ol.2012.689
Pages: 15-21

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Neoadjuvant chemotherapy (NC) for bladder cancer has been reported to significantly improve the 5-year survival rate. The aim of the present study was to examine the roles of ERCC1 and Snail in determining the response to chemotherapy in bladder cancer treated with NC and radical cystectomy (RC). The expression of the Snail and ERCC1 proteins was determined by immunohistochemical staining of specimens obtained from 58 patients with bladder tumors treated with NC and RC. The correlation between clinical response and the expression of Snail and ERCC1 was investigated. Snail and ERCC1 were co-expressed in 24 (41.4%) of the 58 patients. A marked correlation was found between the expression of Snail and ERCC1 (P=0.001). The co-expression of Snail and ERCC1 was not able to predict pathological complete response (P=0.202). Results of the univariate analysis revealed that the co-expression of Snail and ERCC1 predicted shorter disease-free survival (DFS) and overall survival (OS) than the negative expression of Snail and/or ERCC1. Moreover, the co-expression of ERCC1 and Snail was the only predictive factor for both DFS (P=0.029) and OS (P=0.040). The expression of Snail was correlated with that of ERCC1 and the co-expression of Snail and ERCC1 was the only significant predictive factor of shorter DFS and OS in patients with bladder cancer treated with NC and RC.

View Figures

View References

1	Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics. CA Cancer J Clin. 59:225–249. 2009.
2	Committee for Establishment of the Clinical Practice Guidelines for the Management of Bladder Cancer and the Japanese Urological Association. Evidence-based clinical practice guidelines for bladder cancer (summary - JUA 2009 Edition). Int J Urol. 17:102–124. 2010. View Article : Google Scholar : PubMed/NCBI
3	Stenzl A, Cowan NC, De Santis M, et al: The updated EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 55:815–825. 2009. View Article : Google Scholar : PubMed/NCBI
4	Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data. Eur Urol. 48:202–206. 2005. View Article : Google Scholar : PubMed/NCBI
5	Winquist E, Kirchner TS, Segal R, Chin J and Lukka H: Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 171:561–569. 2004. View Article : Google Scholar : PubMed/NCBI
6	Grossman HB, Natale RB, Tangen CM, et al: Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 349:859–866. 2003. View Article : Google Scholar : PubMed/NCBI
7	Matsui Y, Nishiyama H, Watanabe J, et al: The current status of perioperative chemotherapy for invasive bladder cancer: a multiinstitutional retrospective study in Japan. Int J Clin Oncol. 10:133–138. 2005. View Article : Google Scholar : PubMed/NCBI
8	Font A, Taron M, Gago JL, et al: BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer. Ann Oncol. 22:139–144. 2011. View Article : Google Scholar : PubMed/NCBI
9	Pinho MB, Costas F, Sellos J, et al: XAF1 mRNA expression improves progression-free and overall survival for patients with advanced bladder cancer treated with neoadjuvant chemotherapy. Urol Oncol. 27:382–390. 2009. View Article : Google Scholar : PubMed/NCBI
10	Takata R, Katagiri T, Kanehira M, et al: Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapy. Cancer Sci. 98:113–117. 2007. View Article : Google Scholar : PubMed/NCBI
11	Gossage L and Madhusudan S: Current status of excision repair cross complementing-group 1 (ERCC1) in cancer. Cancer Treat Rev. 33:565–577. 2007. View Article : Google Scholar : PubMed/NCBI
12	Park CH, Bessho T, Matsunaga T and Sancar A: Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease. J Biol Chem. 270:22657–22660. 1995. View Article : Google Scholar : PubMed/NCBI
13	Kawashima A, Nakayama M, Kakuta Y, et al: Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer. Clin Cancer Res. 17:2561–2569. 2011. View Article : Google Scholar : PubMed/NCBI
14	Bellmunt J, Paz-Ares L, Cuello M, et al: Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol. 18:522–528. 2007. View Article : Google Scholar
15	Hoffmann AC, Wild P, Leicht C, et al: MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia. 12:628–636. 2010.PubMed/NCBI
16	Kim KH, Do IG, Kim HS, et al: Excision repair cross-complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin-based chemotherapy. APMIS. 118:941–948. 2010. View Article : Google Scholar
17	Matsumura N, Nakamura Y, Kohjimoto Y, et al: The prognostic significance of human equilibrative nucleoside transporter 1 expression in patients with metastatic bladder cancer treated with gemcitabine-cisplatin-based combination chemotherapy. BJU Int. Dec 16–2010.(E-pub ahead of print). View Article : Google Scholar
18	Baumgart E, Cohen MS, Silva Neto B, et al: Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res. 13:1685–1694. 2007. View Article : Google Scholar : PubMed/NCBI
19	McConkey DJ, Choi W, Marquis L, et al: Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 28:335–344. 2009. View Article : Google Scholar : PubMed/NCBI
20	Arumugam T, Ramachandran V, Fournier KF, et al: Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 69:5820–5828. 2009. View Article : Google Scholar : PubMed/NCBI
21	Hsu DS, Lan HY, Huang CH, et al: Regulation of excision repair cross-complementation group 1 by Snail contributes to cisplatin resistance in head and neck cancer. Clin Cancer Res. 16:4561–4571. 2010. View Article : Google Scholar : PubMed/NCBI
22	Sayan AE, Griffiths TR, Pal R, et al: SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proc Natl Acad Sci USA. 106:14884–14889. 2009. View Article : Google Scholar
23	Olaussen KA, Dunant A, Fouret P, et al: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 355:983–991. 2006. View Article : Google Scholar : PubMed/NCBI
24	Bruyere F, Namdarian B, Corcoran NM, et al: Snail expression is an independent predictor of tumor recurrence in superficial bladder cancers. Urol Oncol. 28:591–596. 2010. View Article : Google Scholar : PubMed/NCBI
25	Kosaka T, Kikuchi E, Mikami S, et al: Expression of snail in upper urinary tract urothelial carcinoma: prognostic significance and implications for tumor invasion. Clin Cancer Res. 16:5814–5823. 2010. View Article : Google Scholar : PubMed/NCBI
26	Takata R, Katagiri T, Kanehira M, et al: Predicting response to methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling. Clin Cancer Res. 11:2625–2636. 2005. View Article : Google Scholar
27	Ko JC, Su YJ, Lin ST, et al: Suppression of ERCC1 and Rad51 expression through ERK1/2 inactivation is essential in emodin-mediated cytotoxicity in human non-small cell lung cancer cells. Biochem Pharmacol. 79:655–664. 2010. View Article : Google Scholar : PubMed/NCBI