ObjectiveTo examine the potential role of the neutrophil-to-lymphocyte ratio (NLR) for subclassification of localised upper urinary tract urothelial carcinoma (UUT-UC). Patients and MethodsFrom 2004 to 2010, 234 patients with localised UUT-UC underwent radical nephroureterectomy (RNU). NLRs were only obtained under afebrile conditions before RNU. Patients that underwent neoadjuvant or adjuvant chemotherapy were excluded. The prognostic impact of the NLR was assessed using the log-rank test and multivariate analyses. ResultsOnly advanced pathological stage (>T2) and a NLR of >3 were independently associated with metastasis (P < 0.001 and P = 0.02, respectively) and cancer-specific mortality (P = 0.002 and P = 0.006, respectively). The use of a NLR of >3 further identified a poor prognostic group, especially in patients with T3 UUT-UC for metastasis-free survival and cancer-specific survival (log-rank test, both P < 0.001). ConclusionsFor localised UUT-UC, pathological stage and preoperative NLR independently predict systemic recurrence and cancer-specific death after RNU. Using the NLR for subclassification of T3 UUT-UC seems to further identify a poor prognostic group and may help with clinical decisions about treatment intervention in clinical practice.
The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions. Methods and Results: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells. As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery. Conclusions: Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment.
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