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      DHCR24 predicts poor clinicopathological features of patients with bladder cancer : A STROBE-compliant study

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          Abstract

          To investigate the prognostic value of DHCR24 for patients with bladder cancer (BC). We used public bladder cancer microarray studies to evaluate the expression of DHCR24 between normal bladder tissues and BC cells, to investigate the relationship between the expression of DHCR24 and the clinical features of BC patients. Survival analysis was performed to investigate the correlation between DHCR24 expression and the survivals of BC patients. Gene set enrichment analysis was conducted to identify relevant mechanisms. The results showed that DHCR24 was up-regulated in BC cells compared with that in normal bladder tissues ( P = .0389). Results of chi-square test suggested that BC patients in DHCR24 low expression group were proved to have better clinical characteristics (including tumor grade, disease progression, T staging, and N staging) as compared with those in DHCR24 low expression group ( P < .0001, P = .002, P = .005, and P = .002, respectively). BC patients in DHCR24 low expression group were associated with better cancer-specific survival and overall survival ( P < .0001 and P = .0008, respectively). DHCR24 might promote the proliferation of BC cells through several oncogenesis-associated biological processes (estrogen response, heme metabolism, P53 pathway, cholesterol homeostasis, mTORC1 signaling, peroxisome, xenobiotic metabolism, glycolysis, and protein secretion). Thus, DHCR24 might be a therapeutic target for patients with BC.

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          Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer

          Background While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer. Results We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression. Conclusions We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.
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            Guideline of guidelines: non-muscle-invasive bladder cancer

            Non-muscle invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, however this definition represents a spectrum of disease with a variable clinical course notable for significant risk of recurrence and potential for progression. Management involves risk-adapted strategies of cystoscopic surveillance and intravesical therapy with a goal of bladder preservation when safe to do so. Multiple organizational guidelines exist to help practitioners manage this complicated disease process, however adherence to management principles amongt practicing urologists is reportedly low. We review four major organizational guidelines on NMIBC: American Urological Association (AUA)/Society of Urologic Oncology (SUO), European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE).
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              Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α

              High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4. Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription factor for glucose metabolism, to induce the glycolytic gene expression. JMJD1A was recruited to the promoter of glycolytic gene PGK1 to demethylate H3K9me2. However, the JMJD1A (H1120Y) mutant, which loses the demethylase activity, failed to cooperate with HIF1α to induce the glycolytic gene expression, and failed to demethylate H3K9me2 on PGK1 promoter, suggesting that the demethylase activity of JMJD1A is essential for its coactivation function for HIF1α. Inhibition of glycolysis through knocking down HIF1α or PGK1 decelerated JMJD1A-enhanced UBC cell growth. Consistent with these results, a positive correlation between JMJD1A and several key glycolytic genes in human UBC samples was established by analyzing a microarray-based gene expression profile. In conclusion, our study demonstrates that JMJD1A promotes UBC progression by enhancing glycolysis through coactivation of HIF1α, implicating that JMJD1A is a potential molecular target for UBC treatment.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                September 2018
                28 September 2018
                : 97
                : 39
                : e11830
                Affiliations
                [a ]Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan
                [b ]Department of Cardiology, the First Hospital of Lanzhou University, Lanzhou
                [c ]Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
                Author notes
                []Correspondence: Xing-Huan Wang, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China (e-mail: wangxinghuan1965@ 123456163.com ).
                Article
                MD-D-17-08250 11830
                10.1097/MD.0000000000011830
                6181456
                30278482
                9263701d-a106-4217-821b-fe7f8649dc06
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 29 December 2017
                : 18 July 2018
                Categories
                7300
                Research Article
                Observational Study
                Custom metadata
                TRUE

                bladder cancer,dhcr24,prognostic relevance
                bladder cancer, dhcr24, prognostic relevance

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