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Background: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor‐A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC. Methods: VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR‐299‐3p by real‐time PCR, western blotting, ELISA and dual‐luciferase reporter assays using two UTUC cell lines. The role of miR‐299‐3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro. Results: High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer‐related death and correlated with poor progression‐free and cancer‐specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR‐299‐3p significantly reduced VEGFA protein expression and miR‐299‐3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3′‐UTR. Functional studies indicated that VEGFA overexpression reversed the miR‐299‐3p‐mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR‐299‐3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2. Conclusions: Our findings suggest that miR‐299‐3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR‐299‐3p could be potential therapeutic targets for UTUC. [ABSTRACT FROM AUTHOR]

Visfatin, a newly discovered adipocytokine, is a pro-inflammatory cytokine. This study aimed to evaluate the predictive value of visfatin on prognosis of patients with upper tract urothelial carcinoma. One-hundred and five patients (median age=64, range=24-84 years) were included in this study. Visfatin expression in upper tract urothelial carcinoma tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables using the χ(2) test. The prognostic value of visfatin for recurrence-free and cancer-specific survival was evaluated by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Cox regression model was also used to evaluate the hazard ratios of visfatin on survival. High visfatin expression in upper tract urothelial carcinoma tissues was significantly correlated with tumor stage (P=0.001), grade (P=0.007) and p53 expression (P=0.07). High visfatin expression was associated with poor recurrence-free and cancer-specific survival. Cox regression analysis also revealed that visfatin is an independent predictor of recurrence-free (HR=3.22, P=0.009) and cancer-specific survival (HR=5.74, P=0.023). Our findings indicated that higher visfatin expression is a potential biomarker to predict patient survival. Further study is necessary to investigate the role of visfatin in the carcinogenesis of upper tract urothelial carcinoma.

Background: p53 plays an important role in maintaining genomic stability and regulating the cell cycle. However, the accumulation of p53 protein has been reported to be involved in the carcinogenesis, progression, and metastasis of many types of human cancer. This study evaluates the clinical significance of p53 expression in upper tract urothelial carcinoma., Patients and Methods: One-hundred and twelve cases of upper tract urothelial carcinoma were included in this study. p53 expression was evaluated by immunohistochemistry and the association of p53 expression with clinicopathological variables was analyzed., Results: p53 expression was significantly correlated with patients who were undergoing hemodialysis (p=0.005) and had increased serum creatinine levels (p=0.001). High p53 expression was associated with poor progression-free (p=0.025) and cancer-specific survival (p=0.021), Cox regression analysis also revealed that p53 was an independent predictor of poor progression-free (hazard ratio=3.74, p=0.025) and cancer-specific (hazard ratio=5.87, p=0.030) survival., Conclusion: Our findings indicate that p53 expression is a potential biomarker for predicting patient survival. Further study is necessary to investigate the role of p53 in the carcinogenesis of upper tract urothelial carcinoma.

Background: There are no reliable biomarkers for diagnosis, prediction of outcome or treatment effect monitoring for upper tract urothelial carcinoma (UTUC), which is a uniquely prevalent cancer in Taiwan. In the present study, 128 primary UTUC specimens of various grades and primary tumor status were examined for the expression of cyclooxygenase-2 (COX-2) in tumor and stroma tissues aiming to clarify the association of COX-2 expression with clinical outcomes in Taiwanese patients with UTUC., Materials and Methods: Immunohistochemistry was implemented to investigate COX-2 expression levels in 128 paired tumor and stroma specimens. The association of COX-2 expression with tumor progression and prognosis was analyzed., Results: Our data demonstrated that positive COX-2 expression was more frequent in stromal cells (57.0%), than in tumor sites (53.1%), and the up-regulation of COX-2 was strongly associated with higher cancer-specific death and cancer recurrence rates. In COX-2-negative cases, no similar correlation was found., Conclusion: COX-2 expression was up-regulated in both stromal and tumor cells of more than half of the studied UTUC patients and the positive expression of COX-2 in stromal cells may be a potential predictive and prognostic biomarker for UTUC, especially for cancer-specific death and recurrence.

Background: The DNA non-homologous end-joining repair gene XRCC6 (Ku70) plays a key role in both the DNA double-strand break (DSB) repair and cell cycle arrest. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that a variant in the XRCC6 gene was associated with susceptibility to renal cell carcinoma (RCC)., Materials and Methods: In a hospital-based case-control study of 92 patients with RCC and 580 cancer-free controls, the frequency matched by age and sex, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with RCC risk were investigated in a Taiwanese population. At the same time, 30 adjacent renal tissue samples were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription., Results: Compared with the TT genotype, the TC genotype had a significantly increased risk of RCC [adjusted odds ratio=2.24, 95% confidence interval=1.25-4.08, p=0.0175]. The in vivo mRNA expression in renal tissues revealed a statistically significant lower XRCC6 mRNA expression in samples with TC/CC genotypes compared to those with the TT genotype (p=0.0039)., Conclusion: These evidence suggests that the XRCC6 T-991C genotype together with its mRNA expression are involved in the etiology of RCC and may be a marker for susceptibility to RCC in the population of Taiwan.