SATB1 and Her2 as predictive molecular and immunohistochemical markers for urothelial cell carcinoma of the bladder

2020 ◽  
pp. 1-11
Author(s):  
Samia Hussein ◽  
Anan Fathi ◽  
Nehal S. Abouhashem ◽  
Samar Amer ◽  
Mohamed Hemida ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Lymph Node Involvement ◽  
Genetic Alterations ◽  
Response To Therapy ◽  
Clinicopathological Parameters ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Erbb2 Mrna

Studying bladder cancer molecular biology revealed the presence of genetic alterations. So, detection of molecular biomarkers that help in monitoring the disease, evaluating the prognosis of the patients, and their response to therapy is needed. In this study, we investigated the expression and the prognostic significance of SATB-1 and ERBB2 mRNA and protein by quantitative RT-PCR and immunohistochemical analysis in urothelial bladder cancer cases and the surrounding normal bladder tissue. The correlations between the expression of both markers and the clinicopathological parameters were performed with further analysis of the correlation between the expression of SATB-1 and ERBB2. Compared to control, the expression of SATB-1 and ERBB2 mRNA and protein in cancer tissues were significantly up-regulated (p< 0.05). Also, a positive correlation between both markers was found (r= 0.53, p< 0.001). Moreover, elevated levels of both markers were significantly associated with the stage, lymph node involvement at both mRNA and protein levels (p< 0.001). In conclusion, there is a clinical significance of SATB-1 and ERBB2 as potential biomarkers for predicting bladder cancer patients of aggressive behavior and poor prognosis.

scholarly journals N6-Methylandenosine-Related lncRNAs are Potential Biomarkers for Predicting the Overall Survival Rate of Patients Bladder Cancer

2021 ◽  
Author(s):  
Haihang Zhang ◽  
Panpan Xie ◽  
Kaijia Shi ◽  
Danni Xu ◽  
Xingrui Cai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Value ◽  
Immune Cell ◽  
Cox Regression ◽  
Pearson Correlation ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Bladder Tissue ◽  
Cox Regression Analysis ◽  
Normal Bladder

Abstract Background: The prognostic value of N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) was investigated in 414 bladder cancer (BLCA) and 19 normal bladder tissue samples from The Cancer Genome Atlas (TCGA) datasets. Methods: We implemented Pearson correlation analysis to explore the lncRNAs associated with m6A, and then performed univariate Cox regression analysis to identify nine m6A-associated lncRNAs with prognostic value. The patients with BLCA were divided into two subgroups by consistency clustering. Analysis of the two groups of immune cell infiltration, immune microenvironment and clinical results were significantly different. We identified the prognostic significance of m6A-related lncRNAs by bioinformatic and statistical analysis of data from patients with BLCA.Results: We constructed an m6A-related lncRNA prognostic signature (m6A-LPS, including AL136295.2, AC104564.3, ATP1B3-AS1, EHMT2-AS1 and AC116914.2) to predict the OS of BLCA patients. It is proved that m6A LPS has independent prognostic value.

Expression and prognostic significance of the MMP family molecules in bladder cancer

2020 ◽  
Vol 23 ◽  
Author(s):  
Chong Shen ◽  
La Da ◽  
Zhouliang Wu ◽  
Yujie Wang ◽  
Shen Gao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Prognostic Significance ◽  
Relapse Free Survival ◽  
Poor Overall Survival ◽  
Systematic Analysis ◽  
Free Survival ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Normal Bladder

Background: Bladder cancer (BC) is the 10th most common cancer worldwide with significantly varied prognosis in different pathological subtypes. MMPs, a group of enzymes, could involve in the invasion and metastasis of numerous malignancies. The function of MMPs in BC is partly reported in several studies but with a great conflicts; hence, a systematic analysis of expression levels and prognostic values of these MMP genes are still to be determined. Methods: Firstly, differentially expressed genes (DEGs) of MMPs were identified in ONCOMINE, GEPIA and UALCAN databases; and these DEGs were also detected by real-time RT-qPCR. More importantly, we investigated the clinical significance of these DEGs in BC patients via Kaplan-Meier (KM) Plotter, UALCAN and cBioPortal databases. Results: The study found that mRNA expression of MMP1/11 in BC samples was significantly higher than that in normal bladder tissues, and MMP2/3 were lower in the former than in the latter. The expression level of MMP1/2/7/9/11/13/23B were significantly related to the tumour stages. Furthermore, the prognostic analysis suggested that the high transcription levels of MMP7 and low transcription levels of MMP23A were correlated with favorable relapse-free survival and overall survival in the patients with BC, respectively. Notably, high MMP11/13 expression levels indicated poor overall survival (OS) and relapse-free survival (RFS) in patients with BC. Conclusion: This study revealed that MMP1/2/3/7/9/11/13/23A/23B are possible prognostic biomarkers and clinical therapeutic targets for patients with BC.

A phase 3 randomized study of neoadjuvant chemotherapy (NAC) alone or in combination with nivolumab (NIVO) ± BMS-986205 in cisplatin-eligible muscle invasive bladder cancer (MIBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4587-TPS4587
Author(s):  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Shilpa Gupta ◽  
Gary D. Steinberg ◽  
Juergen E. Gschwend ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Stage ◽  
Randomized Study ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Positive Lymph Node ◽  
Clinical Activity ◽  
Phase 3 ◽  
Bladder Tissue ◽  
Normal Bladder

TPS4587 Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible MIBC, the recommended tx regimen is cisplatin-based NAC prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, suggesting that the PD-1/PD-L1 axis is a valid therapeutic target. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. BMS-986205, a selective, potent, once-daily oral IDO1 inhibitor that works early in the IDO1 pathway to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + BMS-986205 in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± BMS-986205 followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + BMS-986205 (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320.

A phase III randomized study of neoadjuvant chemotherapy (NAC) alone or in combination with nivolumab (NIVO) ± linrodostat mesylate, followed by adjuvant postsurgical NIVO ± linrodostat, in cisplatin-eligible muscle invasive bladder cancer (MIBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5091-TPS5091
Author(s):  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Shilpa Gupta ◽  
Gary D. Steinberg ◽  
Juergen Gschwend ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Randomized Study ◽  
Pathologic Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Muscle Invasive

TPS5091 Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible, muscle invasive BC (MIBC), the recommended tx is cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, supporting the therapeutic pursuit of the PD-1/PD-L1 axis. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. Linrodostat mesylate, a selective, potent, once-daily oral IDO1 inhibitor that works to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + linrodostat in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± linrodostat followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + linrodostat (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320 .

scholarly journals Enhanced Expression of CNTD2/CCNP Predicts Poor Prognosis in Bladder Cancer Based on the GSE13507

2021 ◽  
Vol 12 ◽  
Author(s):  
Mancheng Gong ◽  
Erlin Song ◽  
Guiying Huang ◽  
Wenjun Ni ◽  
Wenjing Dong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Malignant Tumors ◽  
High Expression ◽  
Prognostic Indicators ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Tcga Dataset

Bladder cancer is one of the most common urogenital malignancies in the world, and there are no adequate prognostic indicators. CNTD2 is one of the atypical cyclins, which may be related to the cell cycle and even the development of cancers. Early studies have shown that CNTD2 is closely related to the occurrence and development of many malignant tumors. However, the mechanism of CNTD2 in bladder cancer has not been reported. In our research, we explored the different expressions of CNTD2 between 411 bladder cancers and 19 normal bladder tissues based on the TCGA dataset. CNTD2-related signaling pathways were identified through the GSEA. We analyzed the associations of CNTD2 expression and bladder cancer progression and survival using GSE13507. Compared with 19 cases of normal bladder tissue, CNTD2 gene expression was increased in 411 cases of bladder cancer. The high expression of CNTD2 strongly correlated with grade (P &lt; 0.0001), T classification (P = 0.0001), N classification (P = 0.00011), M classification (P = 0.044), age (P = 0.027), and gender (P = 0.0012). Bladder cancer patients with high CNTD2 expression had shorter overall survival (P &lt; 0.001). In the meantime, univariate and multivariate analyses showed that the increased expression of CNTD2 was an independent factor for poor prognosis in bladder cancer patients (P &lt; 0.001 and P &lt; 0.001, respectively). CNTD2 expression is closely related to bladder cancer progression, and the high expression of CNTD2 may be an adverse biomarker in bladder cancer patients.

scholarly journals A histopathological evaluation of gall bladder cancer with special reference to HER2/neu and E-cadherin in Southern part of Assam

2021 ◽  
Vol 9 (5) ◽  
pp. 1368
Author(s):  
Madhusmita Choudhury ◽  
Gargi Roy Choudhury ◽  
Monoj K. Deka ◽  
Shah A. Sheikh
Keyword(s):  
Bladder Cancer ◽  
Gall Bladder ◽  
Bladder Carcinoma ◽  
Prognostic Significance ◽  
Gall Bladder Cancer ◽  
Clinicopathological Parameters ◽  
Gall Bladder Carcinoma ◽  
Female Ratio ◽  
Her 2 ◽  
E Cadherin

Background/Objective: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. The signs and symptoms of gall bladder arcinoma are not specific and often present late. Diagnosis is, therefore, often made at advanced stage with poorer outcomes. Identifying biomarkers and cancer specific cellular targets, that will pave the way for novel therapeutic approaches and early diagnosis for gall bladder carcinoma, is urgently needed. Proto-oncogenes (HER-2) and E-Cadherin are commonly deregulated in gallbladder cancer (GBC). This study evaluates the prognostic significance of HER-2 and E-Cadherin in GBC patients in Silchar Medical College.Our main objective was to evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival.Methods: A total of 168 cases were received and evaluated for Gall Bladder cancer and control specimens were prospectively collected from 2018-2020. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and E-Cadherin protein expression. The criterion for HER-2 and E-Cadherin positivity was set at 10% and >5% tumor cells showing complete, membranous staining. Clinicopathological correlations were drawn with major clinical outcomes. Results: It was observed that out of 168 cases the male to female ratio is 1:5 with highest number of cases in the age group of 50-59 , i.e., 70 cases with 41.7%. The most common location in this study was fundus with 69% of cases (116 out 0f 168), most commonly presented as biliary colic with 56 number of cases. Grading was also done in 168 cases where most number of cases were moderately differentiated with 86 number of cases with a percentage of 51%. Expression of Her2Neu and E-Cadherin was evaluated where highest number of cases were seen with 1+ score  in the IHC expressions of both the markers with 81 and 61 number of cases respectively. Conclusion: The increasing global incidence, late presentation leading to poor prognosis and lack of effective therapy make the management of gall bladderv carcinoma really challenging. Our study shows the abnormal expression of HER-2 and E-Cadherin expression in gall bladder carcinoma patients in Southern Assam and suggests that  these two markers can be used for potential tool for early detection of gall bladder carcinoma and also can be used for targeted therapy in gall bladder carcinoma.

scholarly journals Identification of Potential Diagnostic Genes for Bladder Cancer by Bioinformatic Analysis

2021 ◽  
Author(s):  
Yongxing Peng ◽  
Minqin Mao ◽  
Zhonglai Li ◽  
Qipeng Xia ◽  
Honghua Tong
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Area Under The Curve ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Diagnostic Efficiency ◽  
Bladder Tissue ◽  
Diagnostic Efficacy ◽  
Normal Bladder

Abstract Background: Cytology and transurethral cystoscopy constitute the gold standard for the diagnosis of bladder cancer (BC). However, some minor lesions cannot be detected in time with these techniques, resulting in a high rate of missed diagnosis. Finding biomarkers that are economical, convenient, sensitive, and specific has become an urgent priority.Methods: Gene expression profile data from BC and normal bladder tissue were downloaded from the Gene Expression Omnibus (GEO) database and used as a training set to screen for differentially expressed genes (DEGs). The bladder gene expression and related clinical data derived from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used as a validation set. The effectiveness of the DEGs as diagnostic criteria was verified in terms of gene expression, gene mutation and diagnostic efficiency.Results: Two upregulated and eight downregulated hub genes were identified by screening. In terms of gene expression, the expression levels of these genes were significantly different between bladder cancer tissues and normal tissues. In terms of clinical diagnostic efficacy, TOP2A had the highest single diagnostic value, while the combinations of TOP2A/CNN1, TOP2A/ISG15/CNN1 and TOP2AISG15/ACTG2 had the largest area under the curve (AUC) among two- or three-indicator combinations.Conclusion: TOP2A, either alone or as part of a combination, has notable diagnostic advantages. However, this still needs to be confirmed in a larger sample with further biological experiments.

scholarly journals MicroRNA-138 Regulates Metastatic Potential of Bladder Cancer Through ZEB2

2015 ◽  
Vol 37 (6) ◽  
pp. 2366-2374 ◽  
Author(s):  
De-Kang Sun ◽  
Jian-Ming Wang ◽  
Peng Zhang ◽  
Yong-Qiang Wang
Keyword(s):  
Bladder Cancer ◽  
Cell Invasion ◽  
Biological Effects ◽  
Metastatic Potential ◽  
Luciferase Reporter ◽  
Bladder Tissue ◽  
Bioinformatics Analyses ◽  
Normal Bladder ◽  
Key Factor ◽  
Normal Bladder Tissue

Background/Aims: The cases of bladder cancer (BC) with poor prognosis largely result from the distal metastases of the primary tumor. Since microRNAs (miRNAs) play critical roles during cancer metastases, determination of the involved miRNAs in the regulation of the metastases of BC may provide novel therapeutic targets for BC treatment. Here, we aimed to study the role of miR-138 in regulation of BC cell invasion and metastases. Methods: We analyzed the levels of miR-138 and ZEB2, a key factor that regulates cancer cell invasion, in the BC specimens from the patients. We also studied the correlation between miR-138 and ZEB2. We performed bioinformatics analyses on the binding of miR-138 to the 3'-UTR of ZEB2 mRNA, and verified the biological effects of this binding through promoter luciferase reporter assay. The effects of miR-138-modification on BC cell invasion were evaluated in a transwell cell invasion assay and a scratch would healing assay. Results: We found that the levels of miR-138 were significantly decreased and the levels of ZEB2 were significantly increased in BC specimens, compared to the paired normal bladder tissue. Metastatic BC appeared to contained lower levels of miR-138. Moreover, miR-138 and ZEB2 inversely correlated in BC specimens. Bioinformatics analyses showed that miR-138 targeted the 3'-UTR of ZEB2 mRNA to inhibit its translation. Furthermore, miR-138 overexpression inhibited ZEB2-mediated cell invasion and metastases, while miR-138 depletion increased ZEB2-mediated cell invasion and metastases in BC cells. Conclusion: Suppression of miR-138 in BC cells may promote ZEB2-mediated cancer invasion and metastases. Thus, miR-138 appears to be an intriguing therapeutic target to prevent metastases of BC.

Presence of CSE1L protein in urine of patients with urinary bladder urothelial carcinomas

2012 ◽  
Vol 27 (3) ◽  
pp. 280-284 ◽  
Author(s):  
Cheng-Jeng Tai ◽  
Ching-Fong Liao ◽  
Tzu-Cheng Su ◽  
Ko-Hung Shen ◽  
Chun-Chao Chang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urinary Bladder ◽  
Tumor Cells ◽  
Chromosome Segregation ◽  
Immunohistochemical Analysis ◽  
High Expression ◽  
Healthy Controls ◽  
Urothelial Carcinomas ◽  
Normal Bladder

The chromosome segregation 1-like (CSE1L) protein is highly expressed in most cancers and has been shown to be secreted by tumor cells. We studied the presence of CSE1L in the urine of patients with bladder urothelial carcinomas. The results of our immunohistochemical analysis showed a high expression of CSE1L in bladder cancer specimens, while the normal bladder specimens only showed a very faint staining in some cells. Immunoblotting showed that CSE1L was present in urine of patients with bladder cancer. Urinary CSE1L-positive cases were detected in 95% (57/60) of patients with bladder urothelial carcinomas or the atypical/suspicious cases with urothelial atypia. No CSE1L was detected in urine of healthy controls (p<0.01). Our results suggest that urinary CSE1L deserves further evaluation for the screening of bladder cancer.

Expression of Beclin 1 in Bladder Cancer and Its Clinical Significance

2013 ◽  
Vol 28 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Gui-hong Liu ◽  
Qian Zhong ◽  
Yun-lin Ye ◽  
Hong-bo Wang ◽  
Li-juan Hu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Histological Grade ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Stage ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Beclin 1 ◽  
Normal Bladder ◽  
Muscle Invasive ◽  
Cancer Tissues

Background The aim of this study is to explore the expression of beclin 1, an autophagy gene, in bladder cancer and to evaluate its clinical and prognostic significance in patients with bladder cancer. Methods Beclin 1 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry in bladder cancer tissues and adjacent normal bladder tissues. The relationship between the expression of beclin 1 and clinicopathological characteristics and prognosis was statistically analyzed. Results mRNA level, protein expression and immunoreactivity of beclin 1 were decreased in bladder cancer tissues compared with adjacent normal tissues. Downregulation of beclin 1 was more frequent in tumors with higher histological grades (the expression of beclin 1 was reduced by 49.0% in G1 and G2, and by 71.8% in G3, p=0.010), and was also reduced by 69.5% in the muscle invasive type and by 51.1% in the non-muscle invasive type (p=0.04). Reduced beclin 1 expression was positively associated with higher histological grade and more advanced clinical stage (p<0.05). Kaplan-Meier survival analysis revealed that patients exhibiting lower beclin 1 expression experienced a shorter survival than those with higher expression (p=0.006). Cox proportional hazards regression analysis showed that beclin 1 protein is an independent predictor of survival (p=0.005). Conclusion Beclin 1 has an influence on the progression of bladder cancer and might serve as a potential prognostic factor for patients with bladder cancer.

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