Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

Background: The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs. Methods: The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC. Results: The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients. Conclusion: To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC

Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2

Abstract Background Uncontrolled proliferation is thought to be the most fundamental characteristic of cancer. Detailed knowledge of cancer cell proliferation mechanisms would not only benefit understanding of cancer progression, but may also provide new clues for developing novel therapeutic strategies. Methods In vitro function of MNX1 (Motor neuron and pancreas homeobox 1) in bladder cancer cell was evaluated using MTT assay, colony formation assay, and bromodeoxyuridine incorporation assay. Real-time PCR and western blotting were performed to detect MNX1 and CCNE1/2 expressions. In vivo tumor growth was conducted in BALB/c-nu mice. Results We reported that MNX1 is responsible for sustaining bladder cancer cell proliferation. Abnormal MNX1 upregulation in bladder cancer cell lines and 167 human tissue specimens; high MNX1 expression levels correlated significantly with shorter 5-year overall and relapse-free survival in the bladder cancer patients. Furthermore, MNX1 overexpression accelerated bladder cancer cell proliferation and tumorigenicity both in vitro and in vivo, whereas MNX1 downregulation arrested it. In addition, MNX1 transcriptionally upregulated CCNE1 and CCNE2 by directly bounding to their promoters, which promoted G1–S transition in the bladder cancer cells. Conclusion These findings reveal an oncogenic role and novel regulatory mechanism of MNX1 in bladder cancer progression and suggest that MNX1 is a potential prognostic biomarker and therapeutic target

RAB20 Promotes Proliferation via G2/M Phase through the Chk1/cdc25c/cdc2-cyclinB1 Pathway in Penile Squamous Cell Carcinoma

RAB20, a member of the RAS GTPase oncogene family, is overexpressed in several cancers with poor outcomes, promoting tumorigenesis and inducing genomic instability. Here, we performed comprehensive genomic sequencing on eight penile squamous cell carcinoma (PSCC) and normal tissue pairs and found that RAB20 was upregulated in tumors, especially in metastatic lymph nodes. RAB20 overexpression in tumors was further verified by qPCR, Western blotting, and immunohistochemistry of our newly established PSCC cell lines and paired tissues. The clinical significance of RAB20 was validated in 259 PSCC patients, the largest cohort to date, and high RAB20 expression positively correlated with the T, N, M status, extranodal extension, and clinical stage (all p p = 0.011, HR = 2.090; 95% Cl: 1.183–4.692), and PSCC patients with high RAB20 expression experienced shorter 5-year cancer-specific survival times (p < 0.001). Furthermore, tumorigenesis assays demonstrated that RAB20 knockdown inhibited cell proliferation, migration, and colony formation in vitro and tumor growth in vivo. RAB20 depletion also induced PSCC cell cycle arrest at G2/M by increasing Chk1 expression and promoting cdc25c phosphorylation to reduce cdc2-cyclinB1 complex formation. Our study revealed an oncogenic role for RAB20 in promoting PSCC cell proliferation at the G2/M phase via the Chk1/cdc25c/cdc2-cyclinB1 pathway. Thus, RAB20 could be a promising prognostic biomarker of advanced PSCC with poor patient survival outcomes and could be a potential therapeutic target

An improved ileal conduit surgery for bladder cancer with fewer complications

Abstract Background Radical cystectomy and urinary diversion remains the standard surgical treatment for patients with muscle-invasive or high-risk or recurrent non-muscle-invasive bladder cancer. Although this approach prolongs patient survival remarkably, there are postoperative complications associated with urinary diversion. This study aimed to assess the efficacy of modified ileal conduit surgery for reducing early and late stoma- and ureteroileal anastomosis-related complications, as compared with conventional ileal conduit urinary diversion. Methods We retrospectively evaluated the clinical data of bladder cancer patients treated with radical cystectomy and ileal conduit urinary diversion at Sun Yat-sen University Cancer Center between January 1, 2000 and June 30, 2016. Ileal conduit was created by the conventional or a modified technique. The clinicopathologic features of the conventional and the modified ileal conduit groups were compared using the t test and the Chi square test. Multivariable logistic regression analysis and multivariable Cox regression analysis were performed to determine the odds of developing stoma- and ureteroileal anastomosis-related complications in the two groups. Results 145 and 100 patients underwent the modified and conventional ileal conduit surgery, respectively. The two groups were comparable with regard to clinicopathologic features. The rate of stoma-related complications was significantly lower in the modified ileal conduit group than in the conventional ileal conduit group (0.7% vs. 17.0%, P < 0.001). No late stoma-related complications were seen in the modified ileal conduit group, but were seen in 13 (13.0%) patients in the conventional ileal conduit group. The rate of ureteroileal anastomosis-related complications was significantly lower in the modified ileal conduit group than in the conventional ileal conduit group (4.8% vs. 15.0%, P = 0.001). In multivariable analyses, the modified ileal conduit group was significantly less likely to develop stoma- (odds ratio [OR] = 0.024, 95% confidence interval [CI] 0.003–0.235; P = 0.001) or ureteroileal anastomosis-related complications (OR = 0.141, 95% CI 0.042–0.476; P = 0.002) than the conventional ileal conduit group. Conclusions Our modified surgical technique for ileal conduit urinary diversion may be effective for reducing early and late complications related to the stoma and the ureteroileal anastomosis. Prospective randomized clinical trials are needed to confirm our results

Additional file 3: of Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2

Figure S1. Pearson score of the indicated cell cycle regulators from cbioportal. (DOCX 83 kb

Additional file 2: of Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2

Table S4. Primers for real-time PCR analysis. Table S5. Primers for plasmid constructs. Table S6. Primers for ChIP. (DOCX 18 kb

Additional file 1: of Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2

Table S1. Clinicopathological characteristics of 167 patient samples. Table S2. Correlation between MNX1 and clinicopathological characteristics of bladder cancer patients. Table S3. Univariate and multivariate analysis of factors associated with overall survival in 167 bladder cancer patients. (DOCX 24 kb