Zhun Wang

YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth

Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a. In normal conditions, AR recruits EZH2 and DNMT3a to YAP1 promoter, thereby promoting DNA methylation and the repression of YAP1 gene transcription. Following ADT treatment or when AR activity is antagonized by Bicalutamide or Enzalutamide, YAP1 gene expression is switched on. In turn, YAP1 promotes SOX2 and Nanog expression and the de-differentiation of PCa cells to stem/progenitor-like cells (PCSC), which potentially contribute to disease recurrence. Finally, the knock down of YAP1 expression or the inhibition of YAP1 function by Verteporfin in TRAMP prostate cancer mice significantly suppresses tumor recurrence following castration. In conclusion, our data reveals that AR suppresses YAP1 gene expression through a novel epigenetic mechanism, which is critical for PCa cells self-renewal and the development of CRPC.

Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis

Background The prognostic value of p53 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic and clinicopathological significance of p53 protein expression in RCC. Materials and Methods Literature was identified from PubMed, Embase, Web of Science, and Cochrane database, which investigated the relationships between p53 expression and outcomes. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with p53 were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Beggs funnel plots and Eggers regression test. Results A total of 2,013 patients from 22 studies were included in the meta-analysis. The results showed that p53 positive expression is associated with poor overall survival (OS) (HR = 2.17, 95% confidence [CI]: 1.51–3.13) and cancer-specific survival (CSS) (HR = 1.59, 95% CI: 1.19–2.12) in RCC. In addition, p53 positive expression was closely correlated with TNM stage (III/IV vs. I/II: OR = 2.51, 95% CI: 1.05–6.00), Fuhrman grade (III/IV vs. I/II: OR = 1.80, 95% CI: 1.24–2.63), and distant metastasis (M1 vs. M0: OR = 1.70, 95% CI: 1.16–2.49), but not related to lymph node involvement (N1 vs. N0: OR = 1.32, 95% CI: 0.80–2.18), primary tumor stage (pT3/pT4 vs. pT1/pT2: OR = 1.16, 95% CI: 0.88–1.53), and sex (n = 2, male vs. female, OR = 1.09, 95% CI: 0.70–1.68). Conclusions This study suggests that p53 positive expression is correlated with poor prognosis and advanced clinicopathological features in patients with RCC, which indicates that p53 is a potentially effective therapeutic target.

Prognostic and clinicopathological value of Ki-67/MIB-1 expression in renal cell carcinoma: a meta-analysis based on 4579 individuals

Background Previous studies have investigated the prognostic significance of Ki-67/MIB-1 expression in renal cell carcinoma (RCC), however, the reports are controversial and inconsistent. This study aimed to investigate Ki-67/MIB-1 expression in RCC and its correlation with prognosis and clinicopathological features. Methods We searched relevant studies that reported associations between Ki-67/MIB-1 expression and prognosis in RCC from PubMed, Embase, Web of Science, and Cochrane Library studies published until April 14, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from eligible studies. Fixed and random effects models were used to calculate pooled HRs and 95% CIs according to heterogeneity. Results A total of 4579 participants from 23 eligible studies were included in this analysis. The results showed that Ki-67/MIB-1 expression was associated with poor overall survival (HR=2.06, 95% CI: 1.64–2.57) and cancer specific survival (HR=2.01, 95% CI: 1.66–2.44). In addition, Ki-67/MIB-1 expression was also correlated with TNM stage (III/IV vs I/II: OR=1.92, 95% CI: 1.61–2.28), pathological T stage (pT3/pT4 vs pT1/pT2: OR=1.56, 95% CI: 1.21–2.02), distant metastasis (M1 vs M0: OR=1.81, 95% CI: 1.34–2.43), and Fuhrman grade (III/IV vs I/II: OR=1.94, 95% CI: 1.21–3.10). Conclusion Our study demonstrates that the presence of high Ki-67/MIB-1 expression and advanced clinicopathological features were correlated with poor prognosis in RCC patients.

Platelet-lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma

BACKGROUND The prognostic value of plated-lymphocyte ratio (PLR) in multiple malignancies had been investigated in previous studies; however, its prognostic value in renal cell carcinoma (RCC) remains controversial. This study was performed to assess the prognostic value of preoperative PLR in RCC patients. METHODS Literature was searched from PubMed, Embase, Web of Science and Cochrane database, which evaluated the relationships between preoperative PLR and prognosis in RCC patients. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Beggs funnel plots and Eggers regression test. RESULTS A total of 1528 patients from seven studies were included in the analysis. The pooled analysis showed that an elevated PLR was an effective prognostic marker of both OS (pooled HR = 2.10, 95%CI: 1.38-3.19, p = 0.001) and PFS (pooled HR = 3.45, 95%CI: 1.61-7.40, p = 0.001). Subgroup analysis revealed that a high PLR significantly predicted worse OS and PFS in Asian studies (OS, pooled HR = 2.72, 95%CI: 1.06-7.03, p = 0.038; PFS, pooled HR = 6.0, 95%CI: 3.12-11.54, p < 0.001), in metastatic RCC patients receiving mixed therapies (OS, pooled HR = 3.69, 95%CI: 1.93-11.42, p = 0.023; PFS, pooled HR = 6.05, 95%CI: 1.34-27.37, p = 0.019) and targeted therapy (OS, pooled HR = 1.59, 95%CI: 0.97-2.62, p = 0.067), in sample size >100 (OS, pooled HR = 1.83, 95%CI: 1.49-2.25, p < 0.001; PFS pooled HR = 6.05, 95%CI: 1.34-27.37, p < 0.019), and in cut-off value of PLR ≤ 195 (OS, pooled HR = 3.65, 95%CI: 1.06-12.60, p = 0.04; PFS pooled HR 4.46, 95%CI: 1.68-11.87, p = 0.003). CONCLUSIONS This study suggests that a high preoperative PLR is correlated with poor prognosis in RCC patients.

Prognostic and clinicopathological value of PBRM1 expression in renal cell carcinoma

BACKGROUND The prognostic value of PBRM1 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconclusive. We investigated the prognostic value and clinicopathological significance of PBRM1 protein expression in RCC. METHODS PubMed, Embase, Web of Science, and Cochrane database were searched for studies investigating the relationships between PBRM1 expression and outcomes in RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Beggs funnel plots and Eggers regression test. RESULTS A total of 2942 patients from 7 studies were included in the meta-analysis. The results showed that decreased expression of PBRM1 is associated with poor overall survival (OS) (HR = 2.11, 95% CI: 1.52-2.96), cancer-specific survival (CSS) (HR = 1.32, 95% CI: 1.10-1.58), and progression-free survival/ recurrence-free survival (PFS/RFS) (HR = 1.57, 95%CI: 1.34-1.85) in RCC. In addition, PBRM1 positive expression was significantly associated with earlier TNM stage (III/IV vs. I/II, OR = 0.53, 95% CI: 0.30-0.94), primary tumor stage (pT3/4 vs. pT1/2, OR = 0.32, 95% CI: 0.20-0.52), and Fuhrman grade (3/4 vs. 1/2, OR = 0.69, 95% CI: 0.46-1.02), but not related to Necrosis or Sex. CONCLUSIONS Decreased expression of PBRM1 is correlated with poor prognosis and advanced clinicopathological features in patients with RCC.

Neutrophil–lymphocyte ratio is a predictor of prognosis in patients with castration-resistant prostate cancer: a meta-analysis

Background The prognostic value of neutrophil–lymphocyte ratio (NLR) in patients with castration-resistant prostate cancer (CRPC) had been investigated in previous studies; however, the results remain inconsistent. This study was aimed to investigate the prognostic value of NLR in CRPC patients. Materials and methods Literature was identified from PubMed, Embase, Web of Science, and Cochrane, which investigated the relationship between pretreatment NLR and prognosis in CRPC patients. HRs for overall survival (OS) and progression-free survival (PFS) were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg’s funnel plot test. Results A total of 5,705 patients from 16 studies were included in this analysis. The pooled results showed that an elevated NLR predict poor OS (pooled HR = 1.52, 95% CI: 1.41–1.63, P<0.001) and PFS (pooled HR = 1.50, 95% CI: 1.21–1.85, P<0.001) in patients with CRPC. Subgroup analysis revealed that an elevated NLR significantly predicted poor OS in Asian studies group (HR = 2.43, 95% CI: 1.47–4.01, P=0.001). The elevated NLR also significantly predicted poor PFS in Asian studies group (HR = 1.99, 95% CI: 1.30–3.06, P=0.002). Conclusion This study suggests that an elevated NLR predict poor prognosis in patients with CRPC.

Giant Pheochromocytoma With Leukemoid Reaction: A Case Report

We present a rare case of silent giant pheochromocytoma with leukemoid reaction that has not been reported before. The patient was a 61-year-old woman who complained of progressive weight loss for 3 months. Preoperatively the urine vanillylmandelic acid was 105.54 mg/24 hours. White blood cell count was 56.9 × 109/L. Abdominal ultrasound and computed tomography revealed a mass measuring 18 × 11 cm in the left adrenal area. The patient underwent adrenal gland neoplasm resection. Postoperative histopathologic evaluation confirmed the diagnosis of pheochromocytoma. The leukocyte dropped to normal gradually in 10 days after the operation. Giant pheochromocytoma with leukemoid reaction was very rare. Resection is the only curative treatment.

C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis

BACKGROUND The prognostic value of C-reactive protein (CRP) in metastatic renal cell carcinoma (RCC) patients receiving tyrosine kinase inhibitors (TKIs) has been investigated in previous studies; however, the results remain inconclusive. This study investigated the prognostic value of pretreatment CRP in patients with metastatic RCC treated with TKIs. METHODS PubMed, Embase, Web of Science, and Cochrane databases were searched for studies investigating the relationships between pretreatment CRP and prognosis in patients with metastatic RCC. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Beggs funnel plots and Eggers regression test. RESULTS A total of 1199 patients from nine studies were included in the analysis. The results showed that an elevated CRP level was an effective prognostic marker of both OS (pooled HR=2.87, 95% confidence interval [CI]: 2.34-3.54, p<0.001) and PFS (pooled HR=2.39, 95% CI: 1.75-3.26, p<0.001). Subgroup analysis revealed that an elevated CRP level significantly predicted poor OS and PFS in studies conducted in Japan (OS, pooled HR=3.03, 95% CI: 2.29-4.01, p<0.001; PFS, pooled HR=3.6, 95% CI: 1.62-8.0, p=0.002), and in cut-off value of CRP <0.8 (OS, pooled HR=2.93, 95% CI: 2.21-3.88, p<0.001; PFS, pooled HR=2.57, 95% CI: 1.82-3.65, p<0.001). CONCLUSIONS This study suggests that an elevated CRP level is correlated with poor prognosis in patients with metastatic RCC receiving TKIs treatment.