Expression and significance of Slit guidance ligand 3 in upper tract urothelial carcinoma

doi:10.3969/j.issn.1006-7795.2020.03.007

Abstract

Abstract: Objective To observe the expression of Slit guidance ligand 3(Slit3) in upper tract urothelial carcinoma (UTUC) and its relationship with the clinicopathological features and prognosis of UTUC patients. Methods The expression of Slit3 in UTUC was detected by immunohistochemical method, and the association of Slit3 expression with the clinicopathological features of UTUC (including age, sex, histological grade, stage and extensive necrosis, etc.) and prognosis were analyzed. Results For UTUC patients, the Slit3 expression decreased with the increased histological grade and tumor stage (P=0.014, P=0.006). Slit3 was also associated with the bladder recurrence (P=0.011). In univariate survival analysis, the lower Slit3 expression was associated with the shorter disease-free survival and cancer-specific survival in UTUC patients (P=0.006, P=0.015), but it was not statistically significant in multivariate analysis (P=0.213, P=0.332). Conclusion Slit3 is likely to be involved in the progression of UTUC. The lower expression of Slit3 is associated with the higher tumor grade, stage and bladder recurrence rate, however, Slit3 is not an independent prognostic factor for UTUC patients.

Key words: upper tract urothelial carcinoma, Slit guidance ligand 3, immunohistochemistry, prognosis

CLC Number:

R737

Wu Xikang, Wang Yue, He Huiying. Expression and significance of Slit guidance ligand 3 in upper tract urothelial carcinoma[J]. Journal of Capital Medical University, 2020, 41(3): 354-359.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2020.03.007

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2020/V41/I3/354

References

[1] Rouprêt M, Babjuk M, Compêrat E, et al. European Association of Urology Guidelines on upper urinary tract Urothelial cell carcinoma:2015 update[J]. Eur Urol, 2015, 68(5):868-879.
[2] Rouprêt M, Babjuk M, Compêrat E, et al. European Association of Urology Guidelines on upper urinary tract urothelial carcinoma:2017 update[J]. Eur Urol, 2018, 73(1):111-122.
[3] Babjuk M, B öhle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder:update 2016[J]. Eur Urol, 2017, 71(3):447-461.
[4] Chung S D, Yu H J, Chueh S C. Re:Ching-Chia Li, Tu-Hao Chang, Wen-Jeng Wu, et al. Significant predictive factors for prognosis of primary upper urinary tract cancer after radical nephroureterectomy in taiwanese patients. Eur Urol 2008;54:1127-35[J]. Eur Urol, 2009, 55(4):e69-70; author reply e71.
[5] Chen X P, Xiong G Y, Li X S, et al. Predictive factors for worse pathological outcomes of upper tract urothelial carcinoma:experience from a nationwide high-volume centre in China[J]. BJU Int, 2013, 112(7):917-924.
[6] Guan H, Wei G, Wu J, et al. Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer[J]. J Clin Endocrinol Metab, 2013, 98(8):E1334-1344.
[7] Denk A E, Braig S, Schubert T, et al. Slit3 inhibits activator protein 1-mediated migration of malignant melanoma cells[J]. Int J Mol Med, 2011, 28(5):721-726.
[8] Yu H, Gao G Z, Jiang L, et al. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer[J]. Int J Clin Exp Pathol, 2013, 6(12):2904-2911.
[9] Paner G P, Stadler W M, Hansel D E, et al. Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers[J]. Eur Urol,2018,73(4):560-569.
[10] Moch H, Cubilla A L, Humphrey P A, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A:renal, penile, and testicular tumours[J]. Eur Urol, 2016, 70(1):93-105.
[11] Rubin M A, Dunn R, Strawderman M, et al. Tissue microarray sampling strategy for prostate cancer biomarker analysis[J]. Am J Surg Pathol, 2002, 26(3):312-319.
[12] Lee H Y, Chen Y J, Li C C, et al. Deduction of novel genes potentially involved in upper tract urothelial carcinoma using next-generation sequencing and bioinformatics approaches[J]. Int J Med Sci, 2019, 16(1):93-105.
[13] Nüsslein-Volhard C, Wieschaus E, Kluding H. Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster:I. Zygotic loci on the second chromosome[J]. Wilehm Roux Arch Dev Biol, 1984, 193(5):267-282.
[14] Rothberg J M, Hartley D A, Walther Z, et al. Slit-an Egf-homologous locus of Drosophila-Melanogaster involved in the development of the embryonic central nervous-system[J]. Cell, 1988, 55(6):1047-1059.
[15] Tong M, Jun T, Nie Y, et al. The role of the Slit/Robo signaling pathway[J]. J Cancer, 2019, 10(12):2694-2705.
[16] Liu J, Zhang L, Wang D, et al. Congenital diaphragmatic hernia, kidney agenesis and cardiac defects associated with Slit3-deficiency in mice[J]. Mech Dev, 2003, 120(9):1059-1070.
[17] Zhang B, Dietrich U M, Geng J G, et al. Repulsive axon guidance molecule Slit3 is a novel angiogenic factor[J].Blood, 2009, 114(19):4300-4309.
[18] Ng L, Chow A K M, Man J H W, et al. Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3beta/beta-catenin pathway[J]. BMC Cancer, 2018, 18(1):621.
[19] Zhang C, Guo H, Li B, et al. Effects of Slit3 silencing on the invasive ability of lung carcinoma A549 cells[J]. Oncol Rep, 2015, 34(2):952-960.
[20] Wei R, Ye X, Zhao Y, et al. MicroRNA-218 inhibits the cell proliferation and migration in clear cell renal cell carcinoma through targeting cancerous inhibitor of protein phosphatase 2A[J]. Oncol Lett, 2019, 17(3):3211-3218.
[21] Kim M, Kim J H, Baek S J, et al. Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes[J]. Int J Oncol, 2016, 48(6):2497-2507.
[22] Moss T J, Qi Y, Xi L, et al. Comprehensive genomic characterization of upper tract urothelial carcinoma[J]. Eur Urol, 2017, 72(4):641-649.