For Physicians Managing Voiding Dysfunction, Improving the Detection Rate of Early Prostate Cancer and Discrimination From Benign Prostatic Hyperplasia, in a Molecular Biomarker Aspects / 대한배뇨장애요실금학회지

Prostate cancer (CaP) is the most common cancer diagnosed among men in the United States and the fifth most common cancer among men in Korea. Unfortunately, the early stages of CaP may have no symptoms. Thus, early detection is very important and physicians managing voiding dysfunction must have awareness about CaP. The traditional tests used for early detection of CaP are the prostate-specific antigen (PSA) blood test and digital rectal examination. However, a high PSA level is not specific for CaP. Benign prostatic hyperplasia, prostatitis, urinary tract infection, and urinary retention can all cause a high PSA level. Thus, no test shows sufficient accuracy to truly be useful for screening men for CaP. A prostate biopsy is the only method that yields a definitive diagnosis of CaP; however, this test is invasive and uncomfortable. Recently, new biomarkers for CaP detection have been proposed to improve the accuracy of the PSA test. In this review, we summarize our knowledge of various new biomarkers, including PSA-associated biomarkers (the prostate health index and 4Kscore), molecular biomarkers (PCA3, TMPRSS2: ERG fusion gene, and various miRNAs), and proteomics-associated biomarkers, and the ways in which they may improve the detection rate of CaP. Accordingly, this review can raise awareness about CaP to physicians managing voiding dysfunction and be a good reference for them.

Predictive Molecular and Protein Markers for the Recurrence of Nonmuscle Invasive Bladder Cancer

Bladder cancer (BC) is the most common urinary tract neoplasm through the world. Around 80% of BC patients present with nonmuscle invasive bladder cancer (NMIBC). Transurethral resection (TUR) of the bladder is the standard treatment to remove cancer tissue from patients with NMIBC. Unfortunately, BC frequently recurs after TUR. At least half of the patients diagnosed with NMIBC experience tumor recurrence after receiving the appropriate treatment. High recurrence rate is one representative characteristic of BC. Therefore, intravesical therapy after TUR is often performed in patients with NMIBC to prevent recurrence. In recent years, various therapeutic agents have been examined in preclinical and clinical trials for use in post-TUR adjuvant intravesical therapy. However, intravesical therapies using anticancer drug are relative safe but, lower anticancer effects and bacillus Calmette-Guérin has a strong anticancer effect but high frequency of adverse events. So, there are growing interests for prediction of recurrence of NMIBC. Until now, many studies were performed for the recurrence prediction markers of NMIBC with cancer tissues instead of blood or urine. In this review, we discuss the predictive value of various genetic, protein markers in cancer tissues, and molecular markers in blood and urine for the recurrence of the NMIBC.

Methylation Signature for Prediction of Progression Free Survival in Surgically Treated Clear Cell Renal Cell Carcinoma

BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.

CDC6 mRNA Expression Is Associated with the Aggressiveness of Prostate Cancer

BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212–7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079–16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

Generation of Whole-Genome Sequencing Data for Comparing Primary and Castration-Resistant Prostate Cancer

Because castration-resistant prostate cancer (CRPC) does not respond to androgen deprivation therapy and has a very poor prognosis, it is critical to identify a prognostic indicator for predicting high-risk patients who will develop CRPC. Here, we report a dataset of whole genomes from four pairs of primary prostate cancer (PC) and CRPC samples. The analysis of the paired PC and CRPC samples in the whole-genome data showed that the average number of somatic mutations per patients was 7,927 in CRPC tissues compared with primary PC tissues (range, 1,691 to 21,705). Our whole-genome sequencing data of primary PC and CRPC may be useful for understanding the genomic changes and molecular mechanisms that occur during the progression from PC to CRPC.

Precision Medicine in Castration-Resistant Prostate Cancer

Prostate cancer is usually managed by androgen deprivation therapy after failure of primary treatment. However, such therapies are only temporarily effective in prostate cancer patients, and the most patients experience the progression to castration-resistant prostate cancer (CRPC). Docetaxel chemotherapy is conventional effective treatment for CRPC but has many adverse effects. In CRPC patients, treatment decisions were not typically base on the recognitions of inter-individual differences. Therefore, there are growing interests for precision medicine in CRPC. In this review, we summarized the precision medicine such as candidate target genes and potential therapies in CRPC.

The Role of MicroRNAs in Oncogenesis and Progression of Prostate Cancer

MicroRNAs (miRNAs) are small noncoding RNAs that target mRNA to reduce gene and protein expression by repressing their targets' translation or inducing mRNA degradation. They play fundamental roles in various cancers, including prostate cancer. Each single miRNA may regulate hundreds of genes, and a certain gene may serve as a target by multiple miRNAs. Hence, miRNAs modulate, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), and metastasis, etc. In this review, we will summarize the several miRNAs that may function as oncogenes and tumor suppressors. And we will describe the each miRNAs associated with cell cycle, apoptosis, EMT, and metastasis in prostate cancer.

Impact of the ASA Physical Status Score on Adjuvant Chemotherapy Eligibility and Survival of Upper Tract Urothelial Carcinoma Patients: a Multicenter Study

The aim of the present multi-institutional study was to assess the influence of the American Society of Anesthesiologists Physical Status (ASA-PS) classification on adjuvant chemotherapy eligibility and survival in a multi-institutional cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed data from 416 patients who underwent RNU for UTUC at four Korean institutions between 2001 and 2013. The ASA-PS classification was obtained from the anesthesia chart. Locally advanced UTUC was defined as ≥ pT3 and/or pN1 disease. The influence of ASA-PS score on survival was evaluated by Kaplan-Meier analyses and a multivariate Cox regression model. Patients with a higher ASA-PS class were less likely to be eligible for adjuvant chemotherapy in locally advanced UTUC (P = 0.016). Kaplan-Meier estimates showed that the high-risk ASA-PS group has a poorer overallsurvival (OS) and cancer-specific survival (CSS) compared to low risk ASA-PS groups in both the total and locally advanced UTUC cohorts. Based on multivariate Cox regression analysis, the high-risk ASA-PS category was an independent predictor for overall mortality (OM) (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.017–3.619; P = 0.044) and cancer-specific mortality (CSM) (HR, 2.120; 95% CI, 1.023–4.394; P = 0.043). In conclusion, high-risk ASA-PS score was independently associated with a lower survival rate in patients with UTUC after RNU. However, the influence of ASA-PS classification on survival was limited to locally advanced UTUC. The lower eligibility of patients in the high-risk ASA category for adjuvant chemotherapy may contribute to the lower survival rate in this group.

Chronological Trends in Clinical and Urinary Metabolic Features over 20 Years in Korean Urolithiasis Patients

Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996–2000, n = 897), group 2 (2001–2005, n = 1,018), group 3 (2006–2010, n = 1,043), and group 4 (2011–2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period.

Efficacy of horse chestnut leaf extract ALH-L1005 as a matrix metalloproteinase inhibitor in ligature-induced periodontitis in canine model

Matrix metalloproteinases (MMPs) are the main proteinases associated with periodontal tissue destruction and remodeling. Therefore, inhibition of host-derived MMPs has a key role in the prevention and reduction of periodontitis progression. Horse chestnut (Aesculus hippocastanum L.) extracts have been used as treatments for inflammatory disease, traditionally. This study assessed the clinical effect as a MMP inhibitor of horse chestnut leaf extract ALH-L1005 on periodontitis. ALH-L1005 was obtained from horse chestnut leaf and its MMP inhibitory activities estimated. Periodontitis was induced in beagles assigned to 4 groups and medicated for 6 weeks: low dose test (LT; ALH-L1005, 100 mg/kg/day), high dose test (HT; ALH-L1005, 200 mg/kg/day), positive control (PC; doxycycline, 10 mg/kg/day), or negative control (NC; placebo). Before and after administration, clinical indices of the teeth and MMP quantity in gingival tissues using zymography were measured. Clinical conditions of the LT, HT, and PC groups were significantly improved after 6 weeks. In zymographic evaluations, gelatinolytic and caseinolytic activities were suppressed in LT, HT, and PC groups but not in the NC group. The results suggest that ALH-L1005 could be an effective agent for clinical prevention and treatment of periodontitis by inhibiting the gelatinase and collagenase activities, which can detach periodontal ligaments from alveolar bone.

The Trend of Uro-Oncologist About Blood Test and Imaging Studies for the Diagnosis of Biochemical Recurrence in Korea

PURPOSE: The aim of this study is to investigate the criteria of biochemical recurrence (BCR) and follow-up periods and methods with and without blood and imaging test of urologic oncology before established guidelines of prostate cancer in Korea. MATERIALS AND METHODS: In December 2015, we sent the questionnaire to urologic oncologist in academic hospital and received the answer from 108 urologic oncologist (50%). Also, we analyzed the data of 1,141 patients underwent radical prostatectomy in 2005 from Korean Medical Insurance. RESULTS: In follow-up, 72 physicians (66.7%) performed blood test every 3 months, 51 physicians (47.2%) performed imaging study in case of BCR. Bone scan was the most common imaging study in the follow-up (74 physicians, 68.5%). But, bone scan was only performed in case of BCR (43 physicians, 39.8%). The criteria of BCR was PSA 0.2 ng/mL (75 physician, 69.4%), 76 physicians (70.4%) was performed different follow-up according to risk of patients. In Korean Medical Insurance data analysis, PSA were performed average 2 times every year and magnetic resonance imaging, computed tomography, Bone scan were performed average 0.1, 0.2, 0.1 times every year, respectively. CONCLUSIONS: The criteria of BCR and the follow-up of prostate cancer patients in Korea were similar Korean prostate cancer guidelines. Blood and imaging test might be increased compared to 10 years ago, it is necessary to compare the Korean Medical Insurance data between 10 years ago and present.

Erratum: Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue / 대한배뇨장애요실금학회지

In this article, a part of fund and grant supports was omitted unintentionally.

In vivo Evaluation of Human Embryonic Stem Cells Isolated by 57-C11 Monoclonal Antibody

BACKGROUND: The normal cells derived from human embryonic stem cells (hESCs) are regarded as substitutes for damaged or dysfunctional adult cells. However, tumorigenicity of hESCs remains a major challenge in clinical application of hESC-derived cell transplantation. Previously, we generated monoclonal antibody (MAb) 57-C11 specific to the surface molecule on undifferentiated hESCs. The aim of this study is to prove whether 57-C11-positive hESCs are pluripotent and tumorigenic in immunodeficient mice. METHODS: Undifferentiated hESCs were mixed with retinoic acid (RA)-differentiated hESCs at different ratios prior to 57-C11-mediated separation. To isolate 57-C11-positive hESCs from the mixture, biotinylated 57-C11 and streptavidin-coated magnetic beads were added to the mixture. Unbound 57-C11-negative hESCs were first isolated after applying magnet to the cell mixture, and 57-C11-bound hESCs were then released from the magnetic beads. In order to measure the efficiency of separation, 57-C11-positive or -negative hESCs were counted after isolation. To evaluate the efficiency of teratoma formation in vivo, 57-C11-positive or negative cells were further injected into left and right, respectively, testes of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. RESULTS: Approximately 77~100% of undifferentiated hESCs were isolated after applying 57-C11-coated magnetic beads to the mixed cell populations. Importantly, teratomas were not observed in NOD/SCID mice after the injection of isolated 57-C11-negative hESCs, whereas teratomas were observed with 57-C11-positive hESCs. CONCLUSION: 57-C11-positive hESCs are pluripotent and tumorigenic. The combination of 57-C11 and magnetic beads will be useful to eliminate remaining undifferentiated hESCs for the safe cell transplantation.

Impact of Young Age at Diagnosis on Survival in Patients with Surgically Treated Renal Cell Carcinoma: a Multicenter Study

The prognostic significance of age in renal cell carcinoma (RCC) is a subject of debate. The aim of the present multi-institutional study was to evaluate the impact of age on clinicopathological features and survival in a large cohort of patients with RCC. A total of 5,178 patients who underwent surgery for RCC at eight institutions in Korea between 1999 and 2011 were categorized into three groups according to age at diagnosis as follows: young age (< 40 years, n = 541), middle-age (≥ 40 and < 60 years, n = 2,551), and old age (≥ 60 years, n = 2,096) groups. Clinicopathological variables and survival rates were compared between the three groups. Young patients had lower stage tumors with a low Fuhrman grade, a lower rate of lymphovascular invasion than patients in the other age groups. Regarding histologic type, the young age group had a lower percentage of clear cell histology and a greater incidence of Xp11.2 translocation RCC. Kaplan-Meier estimates showed that cancer-specific survival was significantly better in the young age group than in the other groups (log rank test, P = 0.008). However, age at diagnosis was not an independent predictor of survival in multivariate analysis. In conclusion, young age at diagnosis was associated with favorable pathologic features, although it was not an independent prognostic factor for survival in patients with surgically-treated RCC. Age itself should not be regarded as a crucial determinant for the treatment of RCC.

Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.

Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue / 대한배뇨장애요실금학회지

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

Lower Levels of Human MOB3B Are Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics

Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P or =10 ng/mL), a Gleason score> or =8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers / 대한배뇨장애요실금학회지

PURPOSE: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. METHODS: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. RESULTS: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. CONCLUSIONS: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.

Clinical and demographic factors associated with compliance and subsequent urinary metabolic changes in first-time ureteral stone formers / 동물의과학연구지

Dietary and lifestyle modifications are widely prescribed to prevent recurrence of urolithiasis, although little is known about the clinical and demographic factors associated with patient compliance and urinary metabolic changes. The present study assessed the clinical and demographic factors influencing compliance with a modified diet and lifestyle in first-time ureteric stone formers as well as determined the effects of compliance on urinary stone risk factors. We retrospectively reviewed the medical records of 53 patients presenting with ureteric calcium stones. Using a self-completed questionnaire, patients were classified according to compliance with seven recommendations for modifying diet and lifestyle into good compliance group (complied with > or = three recommendations) and poor compliance group. Before (on a random diet) and after prescribing the modifications, 24 hour urine samples were collected from those in the good and poor compliance group. The stone size at presentation and initial treatment modality were closely associated with patient compliance (P=0.019, P=0.027, respectively). Citrate excretion significantly increased in the good compliance group after adopting modifications (P=0.012), whereas the poor compliance group did not show a statistically significant difference. Moreover, patients in the poor compliance group showed significantly increased urinary calcium excretion by the end of the study (P=0.040). After adjustments for age, sex, body mass index, and metabolic abnormality status, poor compliance was found to be an independent risk factor for persistence or development of hypocitraturia (OR: 3.885; 95% CI: 1.102~13.694; P=0.035). In conclusion, our results imply that patient education programs regarding diet and lifestyle should be tailored to the individual's clinical and demographic characteristics.

Association of GATA5 methylation with clinocopathological characteristics in non-muscle invasive bladder cancer / 동물의과학연구지

DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, the association between GATA-binding protein 5 (GATA5) methylation and carcinogenesis of various types of tumors was investigated. The aim of the present study was to evaluate the effect of GATA5 methylation status on clinicopathological features and prognosis in primary non-muscle invasive bladder cancer (NMIBC) patients with a long-term followup period. The GATA5 methylation status was determined for 171 human bladder specimens (eight normal controls [NCs] and 163 primary NMIBC patients) using quantitative pyrosequencing analysis. The primary NMIBC tissues were obtained from patients who underwent transurethral resection (TUR) for histologically diagnosed transitional cell carcinomas between 1995 and 2012 at Chungbuk National University Hospital. GATA5 methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates showed significant differences in tumor recurrence and progression according to GATA5 methylation status (each p<0.05). Our results show that increased methylation of GATA5 was significantly associated with not only aggressive characteristics but also poor prognosis in primary NMIBC patients. Alteration of GATA5 methylation might be used as a biomarker for prognosis of NMIBC patients. However, prospective and functional investigations are necessary to clarify the role of GATA5 methylation in future clinical management of patients with NMIBC.