Qilai Long

Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E‐cadherin in renal cell carcinoma

To investigate the molecular mechanism and clinical significance for an oncogenic role of enhancer of zeste homolog 2 (EZH2) in renal cell carcinoma (RCC).

Experience of Mini-Percutaneous Nephrolithotomy in the Treatment of Large Impacted Proximal Ureteral Stones

Objectives: To evaluate the efficacy and safety of mini- percutaneous nephrolithotomy (PCNL) in the treatment of large impacted proximal ureteral stones. Methods: We retrospectively reviewed the outcomes of 163 patients who underwent mini-PCNL between January 2006 and August 2010. Mean age was 48.6 years and mean stone size was 18.4 mm. Hydronephrosis and/or hydroureterosis appeared in all patients. In the prone position, percutaneous access (16-Fr sheath) was established by placement of an access needle into the intended calyx under fluoroscopic guidance or combined with ultrasound guidance for complete obstruction by stones while the contrast agent cannot transit. Pneumatic or ultrasonic probes were used throughout ureterorenoscopy for lithotripsy. The ureteral stents and nephrostomy tube were placed at the end of the procedure. Mean drop in hemoglobin, operative time, success rate, hospital stay, and complications were assessed. Results: Mini-PCNL operations were performed successfully in all patients. Mean operation time was 37 min. Mean postoperative hospital stay was 3.6 days. All cases were followed up for 6-20 months. No major complications like hemorrhage, perforation or organic injury were noted during the operation or postoperatively. The stone-free rate in all patients was 95.7%. Calculus had no recurrence during the follow-up period. Hydronephrosis and hydroureterosis disappeared or were relieved. Conclusions: Mini-PCNL is a safe and effective therapy for large impacted proximal ureteral stones.

Prognostic Value of EZH2 Expression and Activity in Renal Cell Carcinoma: A Prospective Study

Increased expression of EZH2 correlates with aggressive clinical behavior in various malignancies. In this study, we aim to investigate the clinical and prognostic values of EZH2 expression and activity in tumor tissues and improve the risk stratification in patients with renal cell carcinoma after surgery. We analyzed EZH2 expression and its activity as indicated by H3K27me3 levels comprising 373 patients with renal cell carcinoma in our institute. Outcome was assessed as overall survival and disease free survival using Kaplan-Meier analysis. Prognostic values of EZH2 and H3K27me3 expression for clinical outcomes were evaluated by Cox regression analysis. We used receiver operating characteristic to calculate diagnostic accuracy. High EZH2 expression correlates with poor overall survival in all patients, especially in advanced RCC, which is an independent prognostic factor in disease free survival and overall survival. Compared with EZH2, H3K27me3 expression is not an independent prognostic factor. The expressions of H3K27me3 and EZH2 are not completely consistent, which might be due to complicated interaction of Polycomb Repressor Complex 2. A combination of EZH2 expression and TNM stage could have better prognostic value than do TNM stage or EZH2 expression alone in both sets for disease free survival and overall survival. These results imply that evaluating intratumoral EZH2 density might improve prognostic value to the TNM staging system and inform treatment decisions for patients with late-stage renal cell carcinoma.

Mini-flank supra-12th rib incision for open partial nephrectomy compared with laparoscopic partial nephrectomy and traditional open partial nephrectomy.

Purpose The purpose of this study was to report our approach of partial nephrectomy (PN) using a supra-12th rib mini-flank incision. We compared mini-incision open partial nephrectomy (MI-OPN) with open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) to verify whether MI-OPN can be an alternative to OPN and LPN. Methods This was a retrospective single-center study including 194 patients who underwent partial nephrectomy (PN) between February 2005 and December 2010. Demographic, perioperative, and complication data were compared among the MI-OPN group, OPN group and LPN group. Results No statistical differences were reported in either group for age, sex, BMI, tumour side (right or left kidney), RENAL nephrometry scores, PADUA score and preoperative eGFR. The operative time was longer in LPN group when compared with MI-OPN and OPN group (all P<0.001). The warm ischemia time of LPN group was longer than MI-OPN group (P = 0.032) and OPN group (P = 0.005). The length of stay of LPN group was shorter than OPN group (P = 0.018), but was similar to MI-OPN group (P = 0.094). The incidence of renal artery clamping was lower in OPN group when compared with MI-OPN and LPN group (all P<0.001). More estimated blood loss was found in OPN group when compared with MI-OPN group (p = 0.003) and LPN group (P = 0.014). The overall incidence of postoperative complications was similar. Conclusions The approach of MI-OPN can couple the benefits of both minimally invasive and open partial nephrectomy techniques with less estimated blood loss, shorter operative time, shorter length of stay, less postoperative complications, and a smaller incision. MI-OPN may be an effective alternative to laparoscopic or traditional open approaches, which maybe more suitable for the tumors with high RENAL nephrometry score or PADUA score.

Prognostic significance of ST3GAL-1 expression in patients with clear cell renal cell carcinoma

BackgroundAberrant sialylated carbohydrate synthesis is frequently noted in various cancers. Sialyltransferase ST3GAL-1, which adds a sialic acid in an α-2,3 linkage to Gal β1,3 GalNAc, preforms an important role in modulating cellular behaviors. However, little is known about prognostic significance of ST3GAL-1 in clear cell renal cell carcinoma (ccRCC). In this study, we aimed to investigate the prognostic significance of sialyltransferase ST3GAL-1 and its correlation with clinical outcomes in patients with ccRCC.MethodsA total of 286 patients who underwent nephrectomy between 2005 and 2007 in a single academic center were recruited. Immunohistochemical staining was performed on tissue microarrays to assess the expression level. Kaplan-Meier method and Cox proportional hazard model were applied to assess the prognostic value of ST3GAL-1. Nomograms were generated as prediction model for overall survival and disease free survival at 5 and 8 years after nephrectomy.ResultsThe present results show high expression of ST3GAL-1 is associated with reduced overall survival (p = 0.013) and disease free survival (p = 0.004). In multivariate cox analyses, ST3GAL-1 was defined as an independent prognostic factor for overall survival (p = 0.006) and disease free survival (p = 0.001). After incorporation into the University of California Integrated Staging System (UISS) intermediate/high risk group for non-metastatic ccRCC, ST3GAL-1 could further distinguish patient with dismal prognosis (p = 0.015 and 0.002 for OS and DFS respectively). The nomograms revealed better predictive accuracy in predicting 5- and 8- year overall survival and disease free survival than the TNM stage alone.ConclusionsST3GAL-1 is an independent adverse prognostic factor for recurrence and survival of patients with ccRCC.

High Level of Anaphylatoxin C5a Predicts Poor Clinical Outcome in Patients with Clear Cell Renal Cell Carcinoma

Anaphylatoxin C5a, a potent pro-inflammatory peptide produced in the process of complement activation, was proved to have a vital role in tumor initiation and progession by previous investigations. However whether it could act as a prognostic marker remains unknown. Here we retrospectively enrolled 272 ccRCC patients undergoing nephrectomy in Zhongshan Hospital, Shanghai between 2005 and 2007. C5a level was assessed by immunohistochemistry and its association with clinicopathologic features and prognosis were evaluated. Our results indicated that high tumoral C5a level was associated with poor overall survival (OS) (hazard ratio = 1.753, 95% CI 1.068–2.878, P = 0.026). In addition, tumoral C5a could significantly stratify patients’ prognosis both in advanced stage (TNM III + IV) and intermediate/high risk group (SSIGN score ≥4) (P < 0.001 and = 0.008, respectively). Furthermore, incorporating tumoral C5a with other parameters could improve the predicting accuracy, compared with TNM and SSIGN system (c-index = 0.789, 0.713 and 0.727, respectively). In conclusion, tumoral C5a is an independent adverse prognostic biomarker for clinical outcome of ccRCC patients after nephectomy.

Enrichment of C5a-C5aR axis predicts poor postoperative prognosis of patients with clear cell renal cell carcinoma

Anaphylatoxin C5a and its receptor C5aR on cancer cells constitute a vital axis to cancer progression. In this study, we measured C5aR level by immunohistochemistry in the same cohort of our previous C5a research, and C5a-C5aR axis status was determined by synthesizing C5a and C5aR data. C5aR was an adverse independent prognostic factor for ccRCC patients. Kaplan-Meier analyses revealed the unique position of both C5a and C5aR high population in postoperative survival, based on which patients were then shunted into C5a-C5aR enriched and non-enriched groups. Obviously, C5a-C5aR enriched patients significantly had a poorer overall survival (OS) and recurrence free survival (RFS) compared with non-enriched ones, and the independence of C5a-C5aR axis was verified by multivariable analyses (HR 2.118, P = 0.001 for OS, HR 1.715, P = 0.035 for RFS). Established nomograms based on our findings reflected much better predicting accuracy in contrast with most common used TNM and Fuhrman systems. Meanwhile, consistent with HR, C5a-C5aR axis in this study held its advantages over C5a and C5aR for OS prediction by c-index analyses, rather than RFS prediction.

Decreased expression of JMJD3 predicts poor prognosis of patients with clear cell renal cell carcinoma

Previous studies have demonstrated abnormal H3K27 methylation status during clear cell renal cell carcinoma (ccRCC) carcinogenesis, and have suggested that the histone H3K27 demethylases, jumonji domain-containing protein 3 (JMJD3) and ubiquitously-transcribed TPR gene on the X chromosome, are important regulatory factors that alter H3K27 methylation status. The present study aimed to explore the prognostic value of JMJD3 in patients with ccRCC. A total of 331 ccRCC samples were stained for JMJD3 by immunohistochemistry. Stage, Size, Grade and Necrosis (SSIGN) and University of California Los Angeles Integrated Staging System (UISS) scores were applied to stratify risks. Survival analyses were performed through the Kaplan-Meier estimator method and Cox proportional hazard model. The results revealed that JMJD3 expression in ccRCC was significantly increased compared with that in the peritumoral tissue (P<0.001) and negatively associated with a number of other clinicopathological characteristics. Kaplan-Meier estimator and multivariate analyses revealed that decreased tumoral JMJD3 expression was associated with OS (hazard ratio, 2.141; P=0.003), and DFS prediction (hazard ratio, 1.737; P=0.033). In addition, following stratification of patients into three risk levels using the SSIGN and UISS scores, decreased tumoral JMJD3 expression was associated with shorter OS (P=0.003 for SSIGN and UISS scores) and DFS (P=0.007 for SSIGN and P=0.041 for UISS score) in the intermediate risk groups. The results from the present study suggest that JMJD3 is a novel prognostic marker for patients with ccRCC and is of particular significance in patients with intermediate-risk disease.

Prognostic value of copper transporter 1 expression in patients with clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) features a Von Hippel-Lindau mutation, associated with a hypoxia-inducible factor (HIF) imbalance. Copper transporter 1 (CTR1) may also promote tumor progression through the modulation of the HIF pathway by copper. Therefore, the present study explored the prognostic effect of tumor CTR1 expression in patients with ccRCC. A total of 293 patients with ccRCC that underwent nephrectomy were retrospectively enrolled. CTR1 expression was assessed by immunohistochemistry, and its association with clinicopathological features and prognosis were evaluated. The present data indicated that high tumor CTR1 expression was independently associated with poor overall survival (OS) [hazard ratio, 2.291; 95% confidence interval (CI), 1.389–3.777; P<0.001] and disease-free survival (DFS) (hazard ratio, 2.210; 95% CI, 1.299–3.759; P=0.003) rates in patients with ccRCC. Furthermore, CTR1 expression was significantly higher for Mayo Clinic stage, size, grade and necrosis score risk groups, and could be incorporated into several existing prognostic models to improve performance. Nomograms incorporating tumor CTR1 expression with other parameters performed well in the 5- and 8-year OS and DFS rate predictions of patients (concordance index 0.805 and 0.787, respectively). In conclusion, the present study demonstrated that CTR1 expression is a potential independent biomarker for poor prognosis for the recurrence and survival prediction of patients with ccRCC following nephrectomy.

Dot1l expression predicts adverse postoperative prognosis of patients with clear-cell renal cell carcinoma

Background Disruptor of telomeric silencing 1-like (Dot1l), a histone methyltransferase that targets the histone H3 lysine 79 (H3K79), has been reported that its high expression is associated with various cancers, while the association between Dot1l expression and clear-cell renal cell carcinoma (ccRCC) is still unknown. Patients and Methods We retrospectively enrolled 282 patients with ccRCC undergoing nephrectomy from a single institution between 2005 and 2007, with a median follow-up of 99 months. Dot1l expression was evaluated by immunohistochemistry in clinical specimens. We compared the clinical outcomes by Kaplan-Meier survival analyses and assessed the prognostic value of Dot1l expression. Harrells concordance index (C-index) was used to assess the predictive accuracy of different prognostic models. Results Higher Dot1l expression indicated poorer OS (P<0.001) and RFS (P<0.001) in patients with ccRCC. Moreover, Dot1l expression could stratify ccRCC patients in pT stage, Fuhrman grade and SSIGN/ Leibovich subgroups, which might redefine individual risk stratification. Multivariate analyses further indicated that Dot1l expression was an independent prognostic factor for OS (P=0.007) and RFS (P=0.001). The prognostic accuracy of conventional prognostic models was notably improved with Dot1l integration. Two nomograms and calibration plots were built to predict OS and RFS for patients with ccRCC and performed better based on C-index value. Conclusion Dot1l expression is a promising independent prognostic indicator for postoperative recurrence and survival of patients with ccRCC.