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.

PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng
Keyword(s):  
Bladder Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Histological Grade ◽  
Tnm Stage ◽  
Cox Regression Analysis ◽  
Relative Expression ◽  
Kaplan Meier ◽  
Normal Bladder ◽  
Cancer Tissues

Abstract Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.

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 .

Expression of EGFR, HER-2 and p53 predictive of prognosis in muscle-invasive bladder cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15637-15637 ◽  
Author(s):  
W. Sakr ◽  
S. Marur ◽  
M. Che ◽  
L. Heilbrun ◽  
D. Smith ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Survival Data ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Female Ratio ◽  
Her 2 ◽  
Muscle Invasive

15637 Background: The significance of over expression of Erb-1 (epidermal growth factor receptor/ EGFR) and Erb-2 (Her-2) has been reported in various tumors. The aim of this study was to investigate the correlation of the expression of EGFR, Her-2 and p53 with relapse free survival (RFS) and over all survival (OS) in patients with muscle invasive bladder cancer Methods: All patients with muscle invasive bladder cancer diagnosed at our institution between1993and 2004 were considered for the study. Immunohistochemical staining for EGFR, Her2 and p53 performed on formalin-fixed paraffin-embedded archival tissue was evaluated as positive or negative without knowledge of clinical outcome. Survival data determined by reviewing patients medical records were correlated with the staining results. Results: Of the 46 patients who qualified for the study, 40 had slides interpretable for Her 2 and p 53 staining and 38 had slides interpretable for EGFR staining. 35 of 38 were EGFR +ve, 22/40 were Her-2 +ve and 12/40 were p53+ve. The median age of the 46 patients was 67.5 years with a male/female ratio of 60% and 40%. 83% had clinical Stage 2; of those 42%, 23%, and 35% had pathological stages T2, T3 and T4 respectively. Six of 46 (13%), received adjuvant therapy. Tumor histology was pure transitional carcinoma in 56%, or with other components (squamous or adenocarcinoma) in 44%. Median follow-up was 48.8 months for RFS and 44.9 months for OS. Patients with positive EGFR had a median RFS of 34.8 months and median OS of 59.8 months. In patients with negative EGFR, median RFS and OS were not yet reached. Her 2 positive patients had median RFS of 19.2 months compared to 63.8 months in Her-2 negative patients. Her-2 negative patients had median OS of 59.7 months while median was not reached in Her 2 positive patients. Conclusions: While the differences are not statistically significant, the trends observed warrant prospective investigation of the prognostic significance of these markers in a larger population of muscle invasive bladder cancer patients. No significant financial relationships to disclose.

scholarly journals The clinical and prognostic value of CXCL8 in cervical carcinoma patients: immunohistochemical analysis

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Ruiling Yan ◽  
Hanlin Shuai ◽  
Xin Luo ◽  
Xueqin Wang ◽  
Baozhang Guan
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Histological Grade ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Epithelial Cell Lines ◽  
Cancer Tissues ◽  
Microarray Datasets

Cysteine-X-cysteine ligand 8 (CXCL8) was originally discovered as a proinflammatory chemokine. Recently, CXCL8 has been shown to act as an oncogene in several types of human cancers. However, the clinical and prognostic significance of CXCL8 in cervical cancer is poorly understood. In our study, we found that CXCL8 was highly expressed in cervical cancer tissues compared with normal cervical tissues in microarray datasets (GSE9750 and GSE7803). CXCL8 mRNA and protein expressions were increased in cervical cancer tissues and cell lines compared with normal cervical tissues and cervical epithelial cell lines. CXCL8 protein expression was significantly correlated with clinical stage, distant metastasis, histological type, and histological grade. CXCL8 high expression was a poor independent prognostic parameter for cervical cancer patients. In conclusion, CXCL8 is highly expressed in cervical cancer tissues and cell lines, and correlated with malignant status and prognosis in cervical cancer patients.

FADS1 is a Prognostic Biomarker in Bladder Cancer: A Study Based on TCGA Data

2020 ◽  
Vol 23 ◽  
Author(s):  
Ying Lu ◽  
Jing Shao ◽  
Xu Shu ◽  
Yaofei Jiang ◽  
Jianfang Rong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Histological Grade ◽  
Clinical Stage ◽  
Fatty Acid Desaturase ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Normal Tissues ◽  
Potential Biomarker ◽  
T Classification

Aim and Objective: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). Materials and Methods: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October of 2019 in China. Results: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5 ), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020–1.077, p = 0.001). Conclusions: Increased FADS1 expression in bladder cancer is associated with advanced clinical pathological features and may be a potential biomarker for poor prognosis.

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.

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