scholarly journals The Prognostic Significance of Proteasome 26S Subunit, Non-ATPase (PSMD) Genes for Bladder Urothelial Carcinoma Patients

2021 ◽  
Vol 20 ◽  
pp. 117693512110676
Author(s):  
AbdulFattah Salah Fararjeh ◽  
Ali Al-Khader ◽  
Malak Al-Saleem ◽  
Rinad Abu Qauod
Keyword(s):  
Gene Expression ◽  
Urothelial Carcinoma ◽  
Expression Patterns ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Normal Bladder ◽  
Bladder Urothelial Carcinoma ◽  
High Level ◽  
Proteasome 26S

Proteasome a highly sophisticated systems that alter protein structure and function. Proteasome 26S Subunit, Non-ATPase (PSMD) genes have been implicated in several types of malignancies. This is the first study to look at how proteasomal subunits are expressed in patients with bladder urothelial carcinoma (BLCA). BLCA was used to evaluate the predictive value of PSMD genes (PSMD1 to PSMD12) in relation to clinicopathological characteristics. PSMD genes’ expression patterns at the mRNA level were analyzed using a variety of bioinformatics methods, including gene expression profile integrative analysis (GEPIA), Oncomine, TCGA, and Gene expression Omnibus (GEO) databases. The GEPIA and TCGA dataset survival plot functions were used to assess the prognostic significance of PSMD genes. PSMD2, PSMD3, PSMD4, PSMD8, and PSMD11 genes were significantly overexpressed in BLCA compared with normal bladder tissues. PSMD2 and PSMD8 were significantly overexpressed in BLCA more than other types of cancer. High level of PSMD2 and PSMD8 predicted shorter overall (OS) and progression free survival (PFS) in BLCA patients. High level of PSMD2 was significantly associated with elder age ( P  < .001), female gender ( P = .014), tumor grade ( P  < .001), and metastasis ( P = .003). PSMD2 has been shown to be an independent predictor for OS in BLCA patients based on univariate and multivariate analysis ( P  < .001). Overall, according to this study, PSMD2 and PSMD8 could be served as a prognostic biomarker for BLCA patients.

scholarly journals FAM83H and Nectin1 expression are related with survival and relapse of bladder urothelial carcinoma patients

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ae-Ri Ahn ◽  
Sang Jae Noh ◽  
Usama Khamis Hussein ◽  
Ho Sung Park ◽  
Myoung Ja Chung ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Dental Enamel ◽  
Histologic Grade ◽  
Prognostic Indicators ◽  
Free Survival ◽  
Tissue Sections ◽  
Bladder Urothelial Carcinoma

Abstract Background FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. Methods We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. Results Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. Conclusions Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.

scholarly journals Plasticity of gene expression according to salinity in the testis of broodstock and F1 black-chinned tilapia, Sarotherodon melanotheron heudelotii

2014 ◽  
Author(s):  
Jean-Christophe Avarre ◽  
Bruno Guinand ◽  
Rémi Dugué ◽  
Jacky Cosson ◽  
Marc Legendre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Habitat ◽  
Expression Patterns ◽  
Osmotic Tolerance ◽  
Two Generations ◽  
Hypersaline Water ◽  
Significant Expression ◽  
Physiological Impact ◽  
High Level ◽  
Sarotherodon Melanotheron

The black-chinned tilapia Sarotherodon melanotheron heudelotii Rüppell 1852 (Teleostei, Cichlidae) displays remarkable acclimation capacities. When exposed to drastic changes of salinity, which can be the case in its natural habitat, it develops quick physiological responses and keeps reproducing. The present study focused on the physiological impact of salinity on male reproductive capacities, using gene expression as a proxy of acclimation process. Two series of experimental fish were investigated: the first one was composed of fish maintained in freshwater for several generations and newly acclimated to salinities of 35 and 70, whereas the second one consisted of the descendants of the latter born and raised under their native salinity. Expression patterns of 43 candidate genes previously identified from the testes of wild males was investigated in the three salinities and two generations. Twenty of them showed significant expression differences between salinities, and their predicted function revealed that most of them are involved in the osmotic tolerance of sperm cells and/or in the maintenance of sperm motility. A high level of expression variation was evidenced, especially for fish maintained in freshwater. In spite of this, gene expression patterns allowed the differentiation between fish raised in freshwater and those maintained in hypersaline water, in both generations. Altogether, the results presented here suggest that this high variability of expression is likely to ensure the reproductive success of this species under varying salinities.

scholarly journals Characterizing the heterogeneity in 5-aminolevulinic acid–induced fluorescence in glioblastoma

2020 ◽  
Vol 132 (6) ◽  
pp. 1706-1714 ◽  
Author(s):  
Damian A. Almiron Bonnin ◽  
Matthew C. Havrda ◽  
Myung Chang Lee ◽  
Linton Evans ◽  
Cong Ran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Protoporphyrin Ix ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Diagnostic Challenge ◽  
Biological Basis

OBJECTIVE5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods.METHODSThe authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles.RESULTSIn this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors.CONCLUSIONSThese results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment

2003 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Susan Keay ◽  
Francoise Seillier-Moiseiwitsch ◽  
Chen-Ou Zhang ◽  
Toby C. Chai ◽  
Jialu Zhang
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Interstitial Cystitis ◽  
Expression Patterns ◽  
Epithelial Cell Proliferation ◽  
Normal Cells ◽  
Bladder Epithelial Cell ◽  
Normal Bladder

Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [33P]dCTP and hybridized to GeneFilter GF211 microarray membranes (Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC (compared with control) and APF-treated (compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, α2-integrin, α1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, α2-integrin, and α-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.

S109 Prognostic significance of nestin expression in pT1 high-grade bladder urothelial carcinoma patients treated with BCG

2013 ◽  
Vol 12 (4) ◽  
pp. e1217, S109a-e1217, S109d
Author(s):  
V. Şen ◽  
O. Bozkurt ◽  
Ö. Demir ◽  
B. Tuna ◽  
K. Yörükoğlu ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Significance ◽  
High Grade ◽  
Nestin Expression ◽  
Bladder Urothelial Carcinoma

Latent class analysis of bladder urothelial carcinoma to reveal sub-classes defined by alterations to chromatin and signal transduction networks.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 469-469
Author(s):  
Alex Fichtenholtz ◽  
Alyna Khan ◽  
Jeffrey S. Ross ◽  
Siraj Mahamed Ali ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Latent Class Analysis ◽  
Urothelial Carcinoma ◽  
Latent Class ◽  
The United States ◽  
Response To Therapy ◽  
Tumor Type ◽  
Class Analysis ◽  
Bladder Urothelial Carcinoma ◽  
High Level

469 Background: 70,000 new cases of bladder urothelial carcinoma are diagnosed in the United States each year. Previous studies of this disease suggest two divergent pathways of carcinogenesis, with ~70% of cases being driven by alterations in signal transduction pathways (FGFR3, HRAS) and the remainder featuring alterations in cell cycle genes (TP53, RB1). Other studies focus on the high prevalence of alterations in chromatin remodeling genes (ARID1A, CREBBP, EP300) in this tumor type. The relationship between chromatin modifier alterations and the two bladder TCC sub-classes is not yet understood. Methods: Comprehensive genomic profiling (CGP) on 638 clinically confirmed cases of advanced bladder urothelial carcinoma was performed using the FoundationOne platform. The coding exons of 287 cancer-related and 47 introns of 19 genes frequently rearranged in cancer were sequenced and analyzed for base substitutions, insertions, deletions, copy number alterations and select gene fusions. The resultant alteration profiles were analyzed for their information content with an entropy-based approach and the profiles were subjected to hierarchical latent class analysis (LCA). Results: CGP of 488 male and 150 female UCs of median age 66 (min: 29, max: 87) resulted in 3241 detected alterations across 302 unique genes, for a mean of ~5.1 known or likely somatic alterations per sample. The most commonly altered genes were TP53, CDKN2A/B, ARID1A, KDM6A, and MLL2. Information was concentrated in the 33 most frequently altered genes. Multiple high level clusters were defined by combinatorial patterns of alterations in TP53, CDKN2A/B, RB1, and FGFR3. Sub-classes were defined by mutually exclusive alterations in the chromatin modifiers KDM6A, MLL2, and ARID1A. Conclusions: We present a global picture of UC sub-classes that encompasses previously identified local relationships including the mutual exclusivities between FGFR3 and TP53, RB1 and CDKN2A/B, and KDM6A and MLL2. In the context of clinically relevant genomic alterations that auger response to targeted therapies, identification of sub-classes of UC may further delineate response to therapy.

The expression and clinical significance of PD-L1 in patients with upper tract urothelial carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 444-444
Author(s):  
Xinan Sheng ◽  
Zhisong He ◽  
Yan Kong ◽  
Zhihong Chi ◽  
Lu Si ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Tumor Cell ◽  
Urothelial Carcinoma ◽  
Tumor Staging ◽  
Prognostic Significance ◽  
Upper Tract Urothelial Carcinoma ◽  
Tumor Cell Membrane ◽  
Upper Tract ◽  
Bladder Urothelial Carcinoma ◽  
N Classification

444 Background: Primary upper tract urothelial carcinoma (UTUC) is rare. In China UTUCs are more common than in Western populations and account for 20–30% of all TCCs.An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer including bladder urothelial carcinoma. In this study, we investigated the PD-L1 expression and prognostic significance in UTUC. Methods: Formalin-fixed paraffin-embedded tumor samples from 78 patients with upper tract urothelial carcinoma from Peking University Cancer Hospital and Peking Universiy First Hospital were retrieved. PD-L1 expression was evaluated by immunohistochemistry using rabbit monoclonal anti-PD-L1 antibody. PD-L1 positivity on tumor cell membrane was defined as ≥ 1% of tumor cell membrane staining.The clinical data of patients were retrospective collected. The multivariate analysis was used to assess the association of PD-L1 expressionwith tumor staging, pathological N classification, whether firstly diagnosed with metastasis, disease free survival(DFS) and overall survival (OS) in patients. Results: The positive rates of PD-L1 expression were 42.3% (33/78) for upper tract urothelial carcinoma. Sex,location, pathological tumor staging, pathological N classification, whether firstly diagnosed with metastasis did not correlate with PD-L1 expression. In patients with upper tract UC, PD-L1 expression was not associated with DFS and OS on univariate analyses. Conclusions: To our knowledge, this is first study about PD-L1 expression in UTUC patients. In this study, We found the PD-L1 expression in UTUC was higher than in the bladder urothelial carcinoma. It means anti-PD-L1 treatment may be better for advanced UTUC. There was no correlation between PD-L1 expression and outcome.

Molecular profiling of small cell bladder cancer (SCBC) to reveal gene expression determinants of an aggressive phenotype.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4529-4529 ◽  
Author(s):  
Vadim S. Koshkin ◽  
Jordan Reynolds ◽  
Paul Elson ◽  
Cristina Magi-Galluzzi ◽  
Jesse McKenney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Expression Patterns ◽  
Cleveland Clinic ◽  
Molecular Profiling ◽  
Small Cell ◽  
Gene Expression Patterns ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
L1 Protein

4529 Background: SCBC is rare and its underlying biology poorly understood. Molecular profiling can shed light on the biology and identify treatment targets and biomarkers. Methods: A retrospective review of 63 patients (pts) with biopsy-confirmed SCBC at Cleveland Clinic (1994-2015) was performed. Percentage of small cell component (SC%) was defined by independent pathology review. DLL3 and PD-L1 protein expression were measured by IHC in 53 pts. Gene expression analysis was done in 38 primary SCBC tumor samples, 1 metastatic sample, and 5 normal bladder tissue samples (44 total) from the same cohort using HTG EdgeSeq OBP Assay with probes for 2568 genes. Analysis was performed via the RNAseq workflow (Partek Genomics Suite). Results: Among 63 identified pts, median age was 71 (39-90), 83% were men, median SC% was 100% (range 5-100%), median follow-up was 16.6 months and estimated median overall survival (OS) was 22.8 months. Unsupervised hierarchical clustering of gene expression patterns from 44 samples produced 4 distinct clusters. Pts with tumors in cluster 1 (that also included normal samples) did not have metastasis at diagnosis or distant recurrence, both of which were over-represented in the other 3 clusters. Kaplan-Meier analysis revealed a trend towards longer OS in cluster 1 patients (log rank p = 0.065). Higher gene expression of PRC1, NCAM1 (CD56) and DLL3 correlated with higher SC%, as did lower gene expression of ERBB2, PD-L1 and HPGD (p < 0.01). PD-L1 protein expression (≥1% cells) was noted in 30% of pts but did not correlate with outcome, SC%, DLL3 protein expression, or PD-L1 gene expression. DLL3 protein expression (≥1% cells) was noted in 68% of pts and DLL3 > 10% correlated with decreased OS (p = .03). Higher DLL3 protein expression correlated with DLL3 gene expression (Spearman r = 0.70, p < .01) and with SC% (r = .33, p = .01). Conclusions: This is the first study to reveal distinct gene expression patterns that define aggressive behavior, metastatic potential and outcomes in SCBC. The prognostic value of differential gene expression networks and the presence of underlying genomic and epigenetic alterations is the subject of ongoing prospective validation in a larger cohort.

Sign in / Sign up

Export Citation Format

Share Document