The effect of toll like receptors in prognosis in patients undergoing radical cystectomy for bladder cancer.

BACKGROUND: We aimed to evaluate the prognostic significance of TLR4 expression in bladder cancer, its association with genes related to EMT, and the potential regulatory role of selected microRNAs. METHODS AND RESULTS: Tumor and adjacent healthy bladder tissue samples obtained from 25 patients who underwent radical cystectomy for bladder cancer were analysed. The expression levels of TLR4, SPRR2A, SPRR1A, SPRR2B, ZEB2 and CDH1, in addition to miR-200c-3p and miR-146a-5p were measured using the RT-PCR method. Additionally, the expression of the TLR4 protein was assessed using the immunohistochemistry. Gene expression levels were comparatively analysed with regard to their association with the clinicopathological characteristics, and survival. The SPRR2A expression was significantly higher in tumour tissues compared with the levels in normal tissues (p = 0.001). TLR4 expression showed a positive correlation with SPRR1A (r = 0.603,p = 0.001), ZEB2 (r = 0.398, p = 0.049) and CDH1 (r = 0.403, p = 0.046). Notably, TLR4 expression was significantly lower in patients with lymph node metastasis (p = 0.049), while miR-200c-3p expression was considerably lower in patients with a history of smoking (p < 0.0001). Survival analyses revealed an inverse association between overall survival and SPRR2B expression (r = - 0.665,p = 0.013), whereas cancer-related mortality was associated with the decreased expression of SPRR1A (p = 0.008), and SPRR2B (p = 0.005). CONCLUSIONS: TLR4 expression is associated with the regulation of the genes involved in EMT, as well as with metastasis in bladder cancer. The interaction between TLR4, EMT-associated genes and microRNAs may have prognostic and therapeutic implications. However, these findings require validation in prospective larger, independent cohorts.