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Additional File: Uncropped western blot images for Fig 3C

Jie Shen,* Zhen Chen,* Min Fan, Hao Lu, Qianfeng Zhuang, Xiaozhou HeDepartment of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China*These authors contributed equally to this work Background: In recent years, inflammation has become widely recognized as a crucial component in tumor development and progression. Neutrophils are one of the most common inflammatory markers during hematological examinations. The prognostic value of neutrophils in metastatic renal cell carcinoma (mRCC) remains inconsistent. The aim of this meta-analysis is to evaluate the prognostic value of pretreatment neutrophil count in patients with mRCC.Methods: PubMed, Web of Science and Embase were searched for data on the association between pretreatment neutrophil count and mRCC prognosis up to October 7, 2017. We sorted out relevant studies and extracted the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS).Results: A total of 13 studies containing 3,021 patients with mRCC were summarized in the present meta-analysis. An elevated pretreatment neutrophil count yielded a worse OS (HR=2.17, 95% CI=1.68–2.79, P

Zhen Chen,* Kai Wang,* Hao Lu, Dong Xue, Min Fan, Qianfeng Zhuang, Shuai Yin, Xiaozhou He, Renfang Xu Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China *These authors contributed equally to this work Purpose: In the present study, we aimed to evaluate the prognostic significance of the systemic inflammation response index (SIRI), which was defined based on peripheral blood counts of neutrophils, lymphocytes, and monocytes, in patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC).Patients and methods: The prognostic value of SIRI was evaluated in a primary cohort consisting of 414 patients with localized or locally advanced CCRCC and then further validated in an independent cohort composed of 168 patients.Results: Kaplan–Meier survival analyses of both cohorts revealed that CCRCC patients with high SIRI levels exhibited poorer overall survival (OS) and cancer-specific survival (CSS) compared with those with low SIRI levels. Furthermore, univariate and multivariate analyses identified SIRI as a significant independent predictor for both OS (HR: 4.853; 95% CI: 2.362–9.972; P

Qianfeng Zhuang,* Zhen Chen,* Jie Shen,* Min Fan, Dong Xue, Hao Lu, Renfang Xu, Xiaozhou He Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China *These authors contributed equally to this work Background: This meta-analysis evaluated the clinicopathologic and prognostic significance of RASSF1A promoter methylation in renal cell carcinoma (RCC).Materials and methods: The ORs or HRs and their 95% CIs were calculated. Trial sequential analysis was conducted.Results: Twenty-two articles that included 1,421 patients with RCC and 724 controls were identified. RASSF1A promoter methylation correlated with RCC in tissue, blood, and urine samples. On multivariate analysis, RASSF1A promoter methylation was associated with tumor grade (grade 3–4 vs 1–2: OR=3.59), clinical stage (stage 3–4 vs 1–2: OR=2.15), T classification (pT2–4 vs pT1: OR=2.66), histologic subtypes (papillary vs clear cell: OR=2.91), and cancer-specific survival (HR=1.78), but it was not linked to age, gender, lymph node status, distant metastasis, or overall survival. The Cancer Genome Atlas data also showed that RASSF1A methylation was significantly more likely to be seen in papillary vs clear-cell RCC (OR=23.19).Conclusion: RASSF1A promoter methylation may be associated with the development and progression of RCC, as well as poor cancer-specific survival. Methylation was more frequent in papillary vs clear-cell RCC. More studies are needed to confirm these findings in blood or urine samples. Keywords: RAS association domain family protein 1A, methylation, survival, clinical features&nbsp

Objective To assess the safety and efficacy of allograft nephrectomy vs. no-allograft nephrectomy for renal re-transplantation. Methods Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify clinically comparable trials that compared allograft nephrectomy (AN) and no-allograft nephrectomy (no-AN) with renal re-transplantation. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis. Results Eight trials were included involving 1008 patients. Of these, 508 (50.4%) patients underwent AN and 500 (49.6%) had not undergone AN before re-transplantation. The pooled results revealed that the AN group had a longer time interval between graft loss and re-transplantation of 14.40 months (weighted mean difference (WMD) = 11.23; 95% confidence interval (CI): 2.47-19.99; p = 0.01). The AN group also had an higher rate of positive PRA (PRA>10%) before re-transplantation (OR: odds ratio = 1.62, 95% CI = 1.17-2.23, p = 0.003). A comparison of serum creatinine (mg/dL) at one yr after re-transplantation between the groups showed no significant differences (WMD: -0.25; 95% CI: -0.52 to 0.03; p = 0.08). There were neither significant differences in one-yr graft survival rates (OR: 0.74; 95% CI: 0.31-1.72; p = 0.48) nor one-yr patient survival rates (OR: 1.60; 95% CI: 0.57-4.46; p = 0.37) between the groups. Insignificant differences were noted for the rates of acute rejection (OR: 1.30; 95% CI: 0.89-1.91; p = 0.17) and post-operative complications (OR: 1.51; 95% CI: 0.24-9.43; p = 0.66) for the groups. Conclusion Through our meta-analysis, allograft nephrectomy before re-transplantation seemed well tolerated but conferred no significant benefit. The risk-benefit ratio of transplant nephrectomy with re-transplantation must be evaluated in each individual patient.

Xu Han,1,* Lianhua Piao,2,* Qianfeng Zhuang,1 Xiaofeng Yuan,3 Zhiwei Liu,3 Xiaozhou He1 1Department of Urology, The Third Affiliated Hospital of Soochow University, 2Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, 3Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: The growing number of findings demonstrate that nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax domain-containing 3 (NSD3) is amplified and overexpressed in multiple cancer types. Nevertheless, the biological roles of NSD3 in carcinogenesis have not been well understood. In this review, we summarize the current knowledge on the mechanisms underlying NSD3 regulation in different cancers. In addition, NSD3 may serve as a potential druggable target for selective cancer therapy in the future. Keywords: NSD3, cancer, carcinogenesis

Background: To compare the transperitoneal approach with extraperitoneal approach in laparoscopic radical prostatectomy (LRP) (including pure and robotic-assisted LRP) using meta-analytic techniques. Methods: Medline (PubMed), Embase, Ovid, CMB, and Cochrane databases were searched for studies that compared the transperitoneal and extraperitoneal approaches in LRP from January 2000 to January 2017. Outcomes included were operative time, operative bloods joss (milliliters), rate of transfusion, rate of open conversion, rate of intraoperative complications, rate of postoperative complications, and time of postoperative catheterization. Results: Thirteen studies including 1674 patients were selected for the meta-analysis. 850 (50.8%) cases had undergone transperitoneal LRP (TLRP) and 824 (49.2%) cases had undergone the extraperitoneal LRP (ELRP). Comparison of operative time between the TLRP group and the ELRP group showed no significant differences (weighted mean difference [WMD] = 21.21,95%CI = –1.16–43.57, P = .06). No significant differences were observed in blood loss (WMD = −6.04, 95%CI = −43.38–31.29, P = .75) and the rate of transfusion (odds ratio [OR] = 1.03, 95%CI = 0.55–1.96, P = .92) between the 2 groups. No significant differences were observed for the rate of intraoperative complications (OR = 1.25, 95%CI = 0.57–2.21, P = .75) and the rate of open conversion (OR = 1.12, 95%CI = 0.32–4.97, P = .75). Significant differences were observed in the TLRP group compared with the ELRP group (OR = 1.69, 95%CI: 1.23–2.32, P = .001) regarding the rate of postoperative complications. Conclusions: Our meta-analysis findings revealed that the TLRP group showed no significant differences in most important indicators compared with ELRP. Moreover, TLRP showed higher rate of postoperative complications compared with ELRP.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which involved in the degradation of extracellular matrix (ECM) and basement membrane (BM), and associated with tumor invasion and metastasis. Membrane type-2 MMP (MT2-MMP) is a member of MT-MMPs subgroup, and is supposed to be an important step for cancer invasion and metastasis. However, the roles of MT2-MMP in human renal cell carcinoma (RCC) remain unknown. In present study, we identified the roles of MT2-MMP in renal cancer progression by MT2-MMP suppression and overexpression in ACHN cells, which expressed highest level of MT2-MMP and lowest level of MT1-MMP in three kinds of renal cancer cells (786-0, ACHN, OS-RC-2). We found that the expression of MMP-2 could be regulated by MT2-MMP suppression or overexpression in ACHN cells, and both adhesion and invasive activities of ACHN cells were suppressed with MT2-MMP siRNA transfection. In addition, we found that MT2-MMP could increase ACHN cell proliferation, and inhibit cell apoptosis. In vitro tumor growth experiment showed that MT2-MMP could increase clone formation of ACHN cells. The results indicated that MT2-MMP could promoter renal cancer cell invasion and adhesion by activating the expression of MMP2, and stimulate tumor growth of renal cancer.