scholarly journals Impact of Gene Polymorphisms in GAS5 on Urothelial Cell Carcinoma Development and Clinical Characteristics

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 260 ◽  
Author(s):  
Wei-Chun Weng ◽  
Chih-Jung Chen ◽  
Pei-Ni Chen ◽  
Shian-Shiang Wang ◽  
Ming-Ju Hsieh ◽  
...  

Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259–7.324) than did rs145204276 wild type (Ins/Ins) carriers (p  =  0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log–rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.

2015 ◽  
Vol 59 (1) ◽  
pp. 109-112 ◽  
Author(s):  
Shuanzeng Wei ◽  
Zhanyong Bing ◽  
Yuan Yao ◽  
Stephen R. Master ◽  
Prabodh Gupta

Objective: MicroRNAs (miRs) are short noncoding RNA molecules that posttranscriptionally modulate protein expression. There are distinct miR alterations characterizing urothelial cell carcinoma (UCC) of the urinary bladder. Study Design: In this study, we investigate the possibility of using miR as a noninvasive marker in the screening of UCC. The total RNA was extracted from 75 cytology specimens including bladder or renal washings and voided urines. Cases comprise UCC (21 high grade and 6 low grade), 25 normal controls and 23 cases with a history of UCC but negative at the time of testing (negative with a positive history). The expressions of miR-96, miR-182, miR-183, miR-200c, miR-21, miR-141 and miR-30b were determined using quantitative TaqMan real-time PCR. Results and Conclusion: This study shows that the level of miR-182 is higher in cytology specimens from high-grade UCC patients as compared to normal controls. Measuring miR-182 may provide a potential alternative or adjunct approach for screening high-grade UCC.


Author(s):  
Po-Jen Yang ◽  
Ming-Ju Hsieh ◽  
Tung-Wei Hung ◽  
Shian-Shiang Wang ◽  
Shiuan-Chih Chen ◽  
...  

Urothelial cell carcinoma (UCC) is one of the major malignancies of the genitourinary tract, and it is induced by carcinogenic epidemiological risk factors. H19 is one of the most crucial long noncoding RNAs (lncRNAs) and is involved in various types of bladder cancer. In this study, we examined H19 single-nucleotide polymorphisms (SNPs) to investigate UCC susceptibility and clinicopathological characteristics. Using real-time polymerase chain reaction, we analyzed five SNPs of H19 in 431 UCC patients and 431 controls without cancer. The results showed that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants had a high risk of developing muscle invasive tumors (pT2–T4) (p = 0.030; p = 0.025, respectively). With a median follow up of 39 months, CT+TT polymorphisms of rs2107425 were associated with worse disease-specific survival (adjusted hard ratio (AHR) = 2.043, 95% confidence interval (CI) = 1.029-4.059) in UCC patients aged older than 65 years. In conclusion, our results indicate that patients with UCC carrying the H19 rs217727 CT + TT and rs2107425 CT + TT genetic variants have a high risk of developing muscle invasive tumors. Thus, H19 polymorphisms may be applied as a marker or therapeutic target in UCC treatment.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 474-474
Author(s):  
Zachary Hamilton ◽  
Miki Haifler ◽  
Laura-Maria Krabbe ◽  
Timothy N Clinton ◽  
Daniel Han ◽  
...  

474 Background: Upper tract urothelial cell carcinoma (UTUC) is an uncommon malignancy with disparate outcomes. Although use of lymph node dissection (LND) for urothelial cell carcinoma of the bladder has survival benefit even in setting of negative nodal status, therapeutic benefit of LND in the setting of clinical node negative disease for UTUC is unclear. We evaluated survival outcomes for UTUC after LND. Methods: Multicenter retrospective analysis of UTUC patients undergoing nephroureterectomy (NU) for clinical node negative, non-metastatic disease from 2001-2016 (cTis/1-T3N0M0). The cohort was divided based on pathologic lymph node status (pNx, pN0, and pN+). Primary outcome was overall survival (OS). Secondary outcome was recurrence free survival (RFS). Cox regression (CR), logistic regression (LR) and Kaplan−Meier (KMA) analyses were utilized. Results: 191 patients were analyzed (mean age 71.1 years, mean follow up 30.4 months, 27% ureteral location). LND was performed in 40.8% (78) and pN+ was noted in 11.0% (21). Mean number of nodes removed for pN0 = 6.6 and pN+ = 3.9 (p = 0.22). On CR for worsened all-cause mortality, significance was noted for ≥pT2 (OR 1.9, p = 0.031), recurrence (OR 2.3, p = 0.003), and pN+ (OR 2.8, p = 0.004). On KMA, 5 year OS stratified by pathologic node status and nuclear grade (grade 1-2 = LG; grade 3-4 = HG) noted negative survival effect associated with pN+ and HG disease (pN0 LG 85.7%, pN0 HG 41.2%, pNx LG 58.1%, pNx HG 51.1%, pN+ HG 10.7%, log-rank p < 0.001). No patient with pN+ had LG disease. On LR HG disease was predicted only by increasing clinical tumor size (OR 1.3, p = 0.032). No significant difference in complications was noted between the groups (p = 0.1). Conclusions: In clinical node negative disease, LND for UTUC did not have survival benefit; however, LND for UTUC provided prognostic information without significantly increasing risk of complications. Finding of pN+ disease was associated with worsened prognosis. LND may be omitted in LG disease yet should be considered in patients with HG disease and increasing tumor size. Further investigation is requisite.


Author(s):  
Ming-Dow Tsay ◽  
Ming-Ju Hsieh ◽  
Chia-Yi Lee ◽  
Shian-Shiang Wang ◽  
Chuan-Shu Chen ◽  
...  

Fibroblast growth factor receptor 4 (FGFR4) plays a prominent role in cell proliferation and cancer progression. This study explored the effect of FGFR4 single-nucleotide polymorphisms (SNPs) on the clinicopathological characteristics of urothelial cell carcinoma (UCC). This study was conducted to survey the possible correlation of the polymorphism of FGFR4 to the risk and clinicopathologic characteristics of UCC. Four loci of FGFR4 (rs2011077 T > C, rs351855 G > A, rs7708357 G>A, and rs1966265 A > G) were genotyped via the TaqMan allelic discrimination approach in 428 UCC cases and 856 controls. The results indicated that UCC subjects who carried the SNP rs2011077 TC+CC genotypes were significantly related to a higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078–2.846), primary tumor size (OR: 1.637, 95% CI: 1.006–2.662), and histopathologic grading (OR: 1.919, 95% CI: 1.049–3.511). Moreover, the SNP rs1966265 AG+GG genotypes were prominently related to a higher tumor stage (OR: 1.769, 95% CI: 1.082–2.891), primary tumor size (OR: 1.654, 95% CI: 1.011–2.706), and histopathologic grading (OR: 2.006, 95% CI: 1.096–3.674) compared to individuals with AA homozygotes. In conclusion, our data reveal association of FGFR4 polymorphisms with UCC clinicopathologic characteristics. FGFR4 polymorphisms may serve as a marker or therapeutic target in UCC development.


2014 ◽  
Vol 22 (5) ◽  
pp. 408-413
Author(s):  
Carlo Patriarca ◽  
Eva Comperat ◽  
Enrico Bollito ◽  
Agazio Ussia ◽  
Giovanni Scola ◽  
...  

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1412
Author(s):  
Faisal Klufah ◽  
Ghalib Mobaraki ◽  
Axel zur Hausen ◽  
Iryna V. Samarska

BK polyomavirus (BKPyV) has been associated with some high-grade and special urothelial cell carcinoma (UCC) subtypes in immunosuppressed patients. Here, we evaluated the relationship of BKPyV-positive urine cytology specimens (UCS) with UCC. A large single-institution database was retrospectively searched for UCS positive for decoy cells, suggesting BKPyV infection. These were tested for the presence of BKPyV by PCR and immunohistochemistry (IHC) in urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC. Decoy cells were reported in 30 patients out of the database with 22.867 UCS. Of these 30 patients, 16 (53.3%) had no history of UCC. Six patients out of these 16 had a history of transplantation, 4 had a history of severe chronic medical conditions, and 6 had no chronic disease. The other fourteen patients were diagnosed with either in situ or invasive UCC of the urinary bladder (14/30; 46.6%) prior to the detection of decoy cells in the urine. Nine of these UCC patients received intravesical treatment (BCG or mitomycin) after the first presentation with UCC. However, the clinical data on the treatment of the other five UCC patients was lacking. IHC identified BKPyV-positivity in the urine samples of non-UCC and UCC patients, while no BKPyV positivity was found in FFPE tissues of primary UCCs and metastases. In addition, BKPyV-PCR results revealed the presence of BKPyV DNA in the urine of the UCC cases, yet none in the UCC tissues itself. These data strongly indicate that BKPyV reactivation is not restricted to immunosuppression. It can be found in UCS of the immunocompetent patients and may be related to the intravesical BCG or mitomycin treatment of the UCC patients.


2012 ◽  
Vol 96 (4) ◽  
pp. 902-910 ◽  
Author(s):  
Martine M Ros ◽  
H Bas Bueno-de-Mesquita ◽  
Ellen Kampman ◽  
Katja KH Aben ◽  
Frederike L Büchner ◽  
...  

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