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World Journal of Urology

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Open Access 01-11-2020 | Urothelial Cancer | Original Article

Slingshot homolog-1 expression is a poor prognostic factor of pT1 bladder urothelial carcinoma after transurethral resection

Authors: Qiang Luo, Yanxia Liu, Hu Zhao, Peng Guo, Qianwen Wang, Wenjun Li, Gang Li, Bin Wu

Published in: World Journal of Urology | Issue 11/2020

Abstract

Objective

Slingshot homolog-1 (SSH-1) shows an important role in the occurrence and development in various tumors. While, the expression and prognostic implications of SSH-1 in bladder urothelial carcinoma (UC) remain unclear and thus were addressed in this study.

Methods

Immunohistochemistry (IHC) was performed on tissue microarrays composed of 624 bladder UC specimens after transurethral resection of bladder tumor (TUR-BT) to detect SSH-1 expression. The clinic-pathological features were compared between SSH-1( +) and SSH-1(−) subgroups. The Kaplan–Meier curve with log-rank test and univariate/multivariate Cox regression model with stepwise backward elimination methods were performed for survival analyses.

Results

In this study, 359 (57.53%) specimens were detected with SSH-1 expression. SSH-1 positivity was significantly associated with higher pathological grade (p = 0.020), lymphovascular invasion (p = 0.006), tumor recurrence (p < 0.001) and progression (p < 0.001) in bladder UC. Besides, SSH-1 positivity predicted a shorter overall survival (OS, p = 0.024), recurrence-free survival (RFS, p < 0.001), progression-free survival (PFS, p = 0.002) and cancer-specific survival (CSS, p = 0.047). Multivariate Cox proportional hazard analysis showed that tumor size (p = 0.007), lymphovascular invasion (p = 0.003), recurrence (p < 0.001), progression (p < 0.001) and SSH-1 expression (p = 0.015) were predictors of poor prognosis in bladder UC patients.

Conclusions

SSH-1 expression was associated with undesirable clinic-pathological characteristics and poor post-operative prognosis in bladder UC patients. SSH-1 might play an important role in bladder UC and serve as a promising predictor of oncological outcomes in patients with bladder UC.

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F (2017) Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 71(1):96–108CrossRef

Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM et al (2018) Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018. Eur Urol 74(6):784–795CrossRef

Mukherjee P, George AJP, Yadav BK, Jeyaseelan L, Kumar RM, Mukha RP et al (2019) The impact of narrow band imaging in the detection and resection of bladder tumor in transitional cell carcinoma of the bladder: a prospective, blinded sequential intervention randomized controlled Trial. Urology 128:55–61CrossRef

Richards KA, Smith ND, Steinberg GD (2014) The importance of transurethral resection of bladder tumor in the management of nonmuscle invasive bladder cancer: a systematic review of novel technologies. J Urol 191(6):1655–1664CrossRef

Torres RA, Drake DA, Solodushko V, Jadhav R, Smith E, Rocic P et al (2011) Slingshot isoform-specific regulation of cofilin-mediated vascular smooth muscle cell migration and neointima formation. Arterioscl Throm Vasc 31(11):2424–2431CrossRef

Takahashi K, Okabe H, Kanno SI, Nagai T, Mizuno K (2017) A pleckstrin homology-like domain is critical for F-actin binding and cofilin-phosphatase activity of Slingshot-1. Biochem Biophys Res 482(4):686–692CrossRef

Wang Y, Kuramitsu Y, Kitagawa T, Baron B, Yoshino S, Maehara S et al (2015) Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. Cancer Lett 360(2):171–176CrossRef

Maimaiti Y, Maimaitiming M, Li Y, Aibibula S, Ainiwaer A, Aili A et al (2018) SSH1 expression is associated with gastric cancer progression and predicts a poor prognosis. BMC Gastroenterol 18(1):12CrossRef

Aggelou H, Chadla P, Nikou S, Karteri S, Maroulis I, Kalofonos HP et al (2018) LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer progression and chemoresistance. Virchows Arch 472(5):727–737CrossRef

10.

Ramirez-Munoz R, Castro-Sanchez P, Roda-Navarro P (2016) Ultrasensitivity in the cofilin signaling module: a mechanism for tuning T cell responses. Front Immunol 7:59CrossRef

11.

Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM et al (2017) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 71(3):447–461CrossRef

12.

Cumberbatch MGK, Foerster B, Catto JWF, Kamat AM, Kassouf W, Jubber I et al (2018) Repeat transurethral resection in non-muscle-invasive bladder cancer: a systematic review. Eur Urol 73(6):925–933CrossRef

13.

Akand M, Muilwijk T, Raskin Y, De Vrieze M, Joniau S, Van Der Aa F (2019) Quality control indicators for transurethral resection of non-muscle-invasive bladder cancer. Clin Genitourin Cancer 17(4):e784–e792CrossRef

14.

Kassouf W, Aprikian A, Black P, Kulkarni G, Izawa J, Eapen L et al (2016) Recommendations for the improvement of bladder cancer quality of care in Canada: a consensus document reviewed and endorsed by Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Canadian Urological Association (CUA), December 2015. Can Urol Assoc 10(1–2):E46–80CrossRef

15.

Power NE, Izawa J (2016) Comparison of guidelines on non-muscle invasive bladder cancer (EAU, CUA, AUA, NCCN, NICE). Bladder Cancer 2(1):27–36CrossRef

16.

Calo B, Chirico M, Fortunato F, Sanguedolce F, Carvalho-Dias E, Autorino R et al (2019) Is Repeat transurethral resection always needed in high-grade t1 bladder cancer? Front Oncol 9:465CrossRef

17.

Ohta Y, Kousaka K, Nagata-Ohashi K, Ohashi K, Muramoto A, Shima Y et al (2003) Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin. Genes Cells 8(10):811–824CrossRef

18.

Mizuno K (2013) Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation. Cell Signal 25(2):457–469CrossRef

19.

Kurita S, Watanabe Y, Gunji E, Ohashi K, Mizuno K (2008) Molecular dissection of the mechanisms of substrate recognition and F-actin-mediated activation of cofilin-phosphatase Slingshot-1. J Biol Chem 283(47):32542–32552CrossRef

20.

Shishkin S, Eremina L, Pashintseva N, Kovalev L, Kovaleva M (2016) Cofilin-1 and other ADF/cofilin superfamily members in human malignant cells. Int J Mol Sci 18(1):10CrossRef

21.

Palou J, Sylvester RJ, Faba OR, Parada R, Pena JA, Algaba F et al (2012) Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with Bacillus Calmette-Guerin. Eur Urol 62(1):118–125CrossRef

22.

Den V, Cerruto MA, D'Elia C, Brunelli M, Otte O, Minja A et al (2014) Prognostic role of substaging in T1G3 transitional cell carcinoma of the urinary bladder. Mol Clin Oncol 2(4):575–580CrossRef

23.

Gontero P, Sylvester R, Pisano F, Joniau S, Vander Eeckt K, Serretta V et al (2015) Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients. Eur Urol 67(1):74–82CrossRef

24.

Tang Q, Xiong G, Li X, Fang D, Xi C, Zhang L et al (2016) The prognostic impact of squamous and glandular differentiation for upper tract urothelial carcinoma patients after radical nephroureterectomy. World J Urol 34(6):871–877CrossRef

25.

Xu H, Xie L, Liu X, Zhang Y, Shen Z, Chen T et al (2017) Impact of squamous and/or glandular differentiation on recurrence and progression following transurethral resection for non-muscle invasive urothelial carcinoma of bladder. Oncol Lett 14(3):3522–3528CrossRef

26.

Kim SP, Frank I, Cheville JC, Thompson RH, Weight CJ, Thapa P et al (2012) The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. J Urol 188(2):405–409CrossRef

27.

Xylinas E, Rink M, Robinson BD, Lotan Y, Babjuk M, Brisuda A et al (2013) Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy. Eur J Cancer 49(8):1889–1897CrossRef

28.

Mitra AP, Bartsch CC, Bartsch G Jr, Miranda G, Skinner EC, Daneshmand S (2014) Does presence of squamous and glandular differentiation in urothelial carcinoma of the bladder at cystectomy portend poor prognosis? An intensive case-control analysis. Urol Oncol 32(2):117–127CrossRef

Title: Slingshot homolog-1 expression is a poor prognostic factor of pT1 bladder urothelial carcinoma after transurethral resection
Authors: Qiang Luo
Yanxia Liu
Hu Zhao
Peng Guo
Qianwen Wang
Wenjun Li
Gang Li
Bin Wu
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keywords: Urothelial Cancer
Urothelial Cancer
Published in: World Journal of Urology / Issue 11/2020
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-020-03092-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Slingshot homolog-1 expression is a poor prognostic factor of pT1 bladder urothelial carcinoma after transurethral resection

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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