scholarly journals Moesin (MSN) as a Novel Proteome-Based Diagnostic Marker for Early Detection of Invasive Bladder Urothelial Carcinoma in Liquid-Based Cytology

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1018
Author(s):  
Jeong Hwan Park ◽  
Cheol Lee ◽  
Dohyun Han ◽  
Jae Seok Lee ◽  
Kyung Min Lee ◽  
...  
Keyword(s):  
Early Detection ◽  
Urothelial Carcinoma ◽  
Diagnostic Marker ◽  
Three Dimensional ◽  
Biological Significance ◽  
Predictive Biomarker ◽  
Bladder Urothelial Carcinoma ◽  
Potential Biomarker ◽  
Liquid Based Cytology

Bladder urothelial carcinoma (BUC) is the most lethal malignancy of the urinary tract. Treatment for the disease highly depends on the invasiveness of cancer cells. Therefore, a predictive biomarker needs to be identified for invasive BUC. In this study, we employed proteomics methods on urine liquid-based cytology (LBC) samples and a BUC cell line library to determine a novel predictive biomarker for invasive BUC. Furthermore, an in vitro three-dimensional (3D) invasion study for biological significance and diagnostic validation through immunocytochemistry (ICC) were also performed. The proteomic analysis suggested moesin (MSN) as a potential biomarker to predict the invasiveness of BUC. The in vitro 3D invasion study showed that inhibition of MSN significantly decreased invasiveness in BUC cell lines. Further validation using ICC ultimately confirmed moesin (MSN) as a potential biomarker to predict the invasiveness of BUC (p = 0.023). In conclusion, we suggest moesin as a potential diagnostic marker for early detection of BUC with invasion in LBC and as a potential therapeutic target.

scholarly journals The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dexin Shen ◽  
Yayun Fang ◽  
Fenfang Zhou ◽  
Zhao Deng ◽  
Kaiyu Qian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Urothelial Carcinoma ◽  
Carcinoma Cells ◽  
Expression Level ◽  
Tumor Cell Growth ◽  
Migration Ability ◽  
Bladder Urothelial Carcinoma ◽  
Related Proteins

Abstract Background CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.

hSRBC promoter CpG island hypermethylation as resistant predictive biomarker of oxaliplatin based chemotherapy in metastasic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14609-e14609
Author(s):  
Catia Moutinho ◽  
Anna Martinez-Cardus ◽  
Cristina Santos ◽  
Valentín Navarro-Perez ◽  
Eva Martinez-Balibrea ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cpg Island ◽  
Methylation Status ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Promoter Hypermethylation ◽  
Chemotherapeutic Agents ◽  
P Value ◽  
Potential Biomarker

e14609 Background: Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. hSRBC is a tumor suppressor gene whose inactivation has been associated with malignant tumor progression. In a previous work, we investigated the influence of hSRBC promoter methylation alterations in oxaliplatin (OXA) resistance acquisition by using a CRC “in vitro” model, detecting an hSRBC promoter hypermethylation in OXA–resistant derived cells when compared with the sensitive counterpart. These results were validated by functional analyses in the same model. Taking this into account, our aim in the present work is to determine the role of hSRBC methylation status as a potential biomarker of OXA resistance, in metastatic CRC patients, treated at first line with fluouropirimidines plus OXA based chemotherapy. Methods: hSRBC promoter hypermethylation was analyzed in DNA extracted from paraffin embebbed tissue of 111 metastatic CRC tumors by using Methylation Specific PCR. Methylation data was correlated to overall response (OR) and progression free survival (PFS) by using F-Fisher test and Kaplan-Meyer Survival curves respectively. A multivariate analysis was carried out by Cox regression. p-values under 0.05 were considered statistic significant. Results: Two independent cohorts of stage IV CRC tumors were included. Twenty-two out of 111 patients received radical surgery for metastasis, that became to be a positive prognostic factor (p-value = 0.04). Gene hypermethylation was detected in a 33% of cases. Although OR was not associated with hSRBC methylation, we observed a significant correlation between hypermethylation of gene and a worse PFS in patients without metastasis surgery (Log Rank; p-value = 0.04). Conclusions: Remarkably, hSRBC promoter hypermethylation is associated with worse PFS in metastatic CRC patients. We suggest hSRBC methylation status as a predictive biomarker of OXA-based treatment outcome in metastatic CRC patients. However, further studies are warranted in order to elucidate the clinical application of these findings.

scholarly journals A Novel N-Tetrasaccharide in Patients with Congenital Disorders of Glycosylation, Including Asparagine-Linked Glycosylation Protein 1, Phosphomannomutase 2, and Mannose Phosphate Isomerase Deficiencies

2016 ◽  
Vol 62 (1) ◽  
pp. 208-217 ◽  
Author(s):  
Wenyue Zhang ◽  
Philip M James ◽  
Bobby G Ng ◽  
Xueli Li ◽  
Baoyun Xia ◽  
...  
Keyword(s):  
Diagnostic Marker ◽  
Alternative Pathway ◽  
Biological Significance ◽  
Congenital Disorders ◽  
Type I ◽  
Congenital Disorders Of Glycosylation ◽  
Cell Lysate ◽  
Cultured Skin ◽  
Phosphomannomutase 2

Abstract BACKGROUND Primary deficiencies in mannosylation of N-glycans are seen in a majority of patients with congenital disorders of glycosylation (CDG). We report the discovery of a series of novel N-glycans in sera, plasma, and cultured skin fibroblasts from patients with CDG having deficient mannosylation. METHOD We used LC-MS/MS and MALDI-TOF-MS analysis to identify and quantify a novel N-linked tetrasaccharide linked to the protein core, an N-tetrasaccharide (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) in plasma, serum glycoproteins, and a fibroblast lysate from patients with CDG caused by ALG1 [ALG1 (asparagine-linked glycosylation protein 1), chitobiosyldiphosphodolichol β-mannosyltransferase], PMM2 (phosphomannomutase 2), and MPI (mannose phosphate isomerase). RESULTS Glycoproteins in sera, plasma, or cell lysate from ALG1-CDG, PMM2-CDG, and MPI-CDG patients had substantially more N-tetrasaccharide than unaffected controls. We observed a >80% decline in relative concentrations of the N-tetrasaccharide in MPI-CDG plasma after mannose therapy in 1 patient and in ALG1-CDG fibroblasts in vitro supplemented with mannose. CONCLUSIONS This novel N-tetrasaccharide could serve as a diagnostic marker of ALG1-, PMM2-, or MPI-CDG for screening of these 3 common CDG subtypes that comprise >70% of CDG type I patients. Its quantification by LC-MS/MS may be useful for monitoring therapeutic efficacy of mannose. The discovery of these small N-glycans also indicates the presence of an alternative pathway in N-glycosylation not recognized previously, but its biological significance remains to be studied.

scholarly journals Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker

Neoplasia ◽  
2018 ◽  
Vol 20 (4) ◽  
pp. 364-373 ◽  
Author(s):  
Wei Tse Li ◽  
Hao Zheng ◽  
Vincent Nguyen ◽  
Jessica Wang-Rodriguez ◽  
Weg M. Ongkeko
Keyword(s):  
Functional Genomics ◽  
Urothelial Carcinoma ◽  
Bladder Urothelial Carcinoma ◽  
Potential Biomarker

scholarly journals A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiao-chen Luan ◽  
Teng-yue Zeng ◽  
Qi-jie Zhang ◽  
De-run Xia ◽  
Rong Cong ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Cell ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Prognostic Analysis ◽  
Regulated Cell Death ◽  
Bladder Urothelial Carcinoma ◽  
Prediction Of Prognosis ◽  
Pathway Analyses

Abstract Background Ferroptosis, a novel form of regulated cell death, has been implicated in the pathogenesis of cancers. Nevertheless, the potential function and prognostic values of ferroptosis in bladder urothelial carcinoma (BLCA) are complex and remain to be clarified. Therefore, we proposed to systematically examine the roles of ferroptosis-associated genes (FAGs) in BLCA. Methods According to The Cancer Genome Atlas (TCGA) database, differently expressed FAGs (DEFAGs) and differently expressed transcription factors (DETFs) were identified in BLCA. Next, the network between DEFAGs and DETFs, GO annotations and KEGG pathway analyses were performed. Then, through univariate, LASSO and multivariate regression analyses, a novel signature based on FAGs was constructed. Moreover, survival analysis, PCA analysis, t-SNE analysis, ROC analysis, independent prognostic analysis, clinicopathological and immune correlation analysis, and experimental validation were utilized to evaluate the signature. Results Twenty-eight DEFAGs were identified, and four FAGs (CRYAB, TFRC, SQLE and G6PD) were finally utilized to establish the FAGs based signature in the TCGA cohort, which was subsequently validated in the GEO database. Moreover, we found that immune cell infiltration, immunotherapy-related biomarkers and immune-related pathways were significantly different between two risk groups. Besides, nine molecule drugs with the potential to treat bladder cancer were identified by the connectivity map database analysis. Finally, the expression levels of crucial FAGs were verified by the experiment, which were consistent with our bioinformatics analysis, and knockdown of TFRC could inhibit cell proliferation and colony formation in BLCA cell lines in vitro. Conclusions Our study identified prognostic ferroptosis-associated genes and established a novel FAGs signature, which could accurately predict prognosis in BLCA patients.

Galectin-9 as a prognostic and predictive biomarker in bladder urothelial carcinoma

2017 ◽  
Vol 35 (6) ◽  
pp. 349-355 ◽  
Author(s):  
Yidong Liu ◽  
Zheng Liu ◽  
Qiang Fu ◽  
Zewei Wang ◽  
Hangcheng Fu ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Predictive Biomarker ◽  
Bladder Urothelial Carcinoma
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