scholarly journals Upregulation of Versican Associated with Tumor Progression, Metastasis, and Poor Prognosis in Bladder Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qi Zhang ◽  
Junxiu Wu ◽  
Xinpeng Chen ◽  
Ming Zhao ◽  
Dahong Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Poor Prognosis ◽  
Molecular Subtype ◽  
Histological Grade ◽  
Mrna Level ◽  
Human Bladder ◽  
Clinical Prognosis ◽  
Ecm Remodeling ◽  
Kaplan Meier

Objective. This work analyzes the role of versican (VCAN) on bladder cancer (BLCA). Versican (VCAN) is a chondroitin sulfate proteoglycan which is important for tumorigenesis and the development of cancer. However, the expression of VCAN on human bladder cancer (BLCA) has been rarely reported. Methods. The clinical significance of VCAN in BLCA has been determined by our bioinformatics tools. Then, we performed immunohistochemical staining (IHC) and analyzed the correlation between VCAN expression and clinicopathological features. Results. The bioinformatics results reveal that a high VCAN mRNA level was significantly associated with stage, histological subtype, molecular subtype, and metastasis in BLCA. Furthermore, IHC reveals that expression of VCAN was significantly correlated with the number of tumors, invasion depth, lymph node metastasis, distant metastasis, and histological grade. Kaplan-Meier survival analysis reveals that patients with a high expression of VCAN have poor prognosis than those patients with a low expression of VCAN. According to our result from the bioinformatics database, the mechanism of VCAN in BLCA revealed that VCAN was related to FBN1 and genes of the ECM remodeling pathway (MMP1, MMP2). Conclusion. VCAN expression might be included in the process of carcinogenesis and prognosis. Hence, VCAN could be a reliable biomarker of the clinical prognosis on BLCA.

scholarly journals TMIC-03. UPREGULATION OF THE NLRC4 INFLAMMASOME CONTRIBUTES TO POOR PROGNOSIS IN GLIOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi247-vi247
Author(s):  
Jaejoon Lim ◽  
Youngjoon Park ◽  
Minjun Kim ◽  
Juwon Ahn ◽  
KyuBum Kwack ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Tumor Development ◽  
The Cancer Genome Atlas ◽  
Immune Functions ◽  
Potential Therapeutic Target ◽  
Clinical Prognosis ◽  
Tumor Microenvironments ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

scholarly journals Epigenetic regulation of mammalian Hedgehog signaling to the stroma determines the molecular subtype of bladder cancer

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
SungEun Kim ◽  
Yubin Kim ◽  
JungHo Kong ◽  
Eunjee Kim ◽  
Jae Hyeok Choi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Molecular Subtype ◽  
Early Stage ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Stromal Response

In bladder, loss of mammalian Sonic Hedgehog (Shh) accompanies progression to invasive urothelial carcinoma, but the molecular mechanisms underlying this cancer-initiating event are poorly defined. Here, we show that loss of Shh results from hypermethylation of the CpG shore of the Shh gene, and that inhibition of DNA methylation increases Shh expression to halt the initiation of murine urothelial carcinoma at the early stage of progression. In full-fledged tumors, pharmacologic augmentation of Hedgehog (Hh) pathway activity impedes tumor growth, and this cancer-restraining effect of Hh signaling is mediated by the stromal response to Shh signals, which stimulates subtype conversion of basal to luminal-like urothelial carcinoma. Our findings thus provide a basis to develop subtype-specific strategies for the management of human 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.

scholarly journals Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Interferon-Induced Apoptosis in Human Bladder Cancer Cells

2004 ◽  
Vol 64 (24) ◽  
pp. 8973-8979 ◽  
Author(s):  
Angela Papageorgiou ◽  
Laura Lashinger ◽  
Randall Millikan ◽  
H. Barton Grossman ◽  
William Benedict ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Induced Apoptosis ◽  
Human Bladder Cancer Cells ◽  
Necrosis Factor

Analysis of Variance Based Significance Analysis of Cartilage Tumor

2020 ◽  
Vol 10 (9) ◽  
pp. 1985-1991
Author(s):  
Yuan Li ◽  
Zili Xu ◽  
Xiangyang Liu ◽  
Xiandong Peng ◽  
Shu Cao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Poor Prognosis ◽  
Histological Grade ◽  
Stage I ◽  
Stage Iii ◽  
Ajcc Stage ◽  
Kaplan Meier ◽  
First Choice ◽  
Clinicopathological Significance ◽  
Enneking Stage

Chondrosarcoma is a malignant bone tumor with poor prognosis. Surgical treatment is the first choice for chondrosarcomas. Chondrosarcoma is not sensitive to chemotherapy and radiotherapy. Identification of biological markers is important for the early diagnosis and targeted treatment of chondrosarcoma. This study aimed to investigate the protein expression and clinicopathological significance of APEX1 and Haptoglobin in 85 chondrosarcomas and 38 osteochondromas based on deep learning. The APEX1 and Haptoglobin protein expression in tissues was measured by immunohistochemistry. The percentage of positive APEX1 and Haptoglobin expression was significantly higher in patients with chondrosarcoma than in patients with osteochondroma (P < 0001). The percentage of positive APEX1 and Haptoglobin expression was significantly lower in patients with histological grade I, AJCC stage I, Enneking stage I and non-metastatic chondrosarcoma than patients with histological grade III, AJCC stage III+IV, Enneking stage III, and metastatic chondrosarcoma (P < 0005 or P < 0001). APEX1 expression was positively correlated with Haptoglobin expression in chondrosarcoma (P < 0001). Kaplan—Meier survival analysis demonstrated that histological grade, AJCC stage, Enneking stage, metastasis, invasion, and APEX1 and Haptoglobin expression significantly correlated with a short mean survival time of patients with chondrosarcoma (P < 0005 or P < 0001). Cox multivariate analysis showed that positive APEX1 and Haptoglobin expressions were independent prognostic factors that negatively correlated with postoperative survival and positively correlated with mortality. The AUC for APEX1 (AUC = 0.673, 95% CI: 0.573—0.772), or Haptoglobin (AUC = 0.649, 95% CI: 0.548—0.750), respectively. Positive APEX1 and Haptoglobin expression is associated with the carcinogenesis, progression and poor prognosis of chondrosarcoma.

Novel oncogenic function of ATDC in bladder cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4591-4591
Author(s):  
Phillip Lee Palmbos ◽  
Lidong Wang ◽  
Huibin Yang ◽  
Taylor Detzler ◽  
Gina Ney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Pten Expression ◽  
Cancer Tissue ◽  
Bladder Tumors ◽  
Human Bladder ◽  
Urothelial Carcinomas ◽  
Normal Bladder

4591 Background: Bladder cancer is a common and deadly disease, but the molecular events leading to its initiation and progression are incompletely understood. We recently identified Ataxia-Telangiectasia Group D Associated (ATDC) as a novel oncogene which drives tumor proliferation and invasion in pancreatic carcinoma (Cancer Cell, 2009). In this study, we describe the role of ATDC as an oncogene in bladder cancer. Methods: To further determine the oncogenic role of ATDC, we generated ATDC transgenic (tg) mice in which ATDC expression was driven by a CMV promoter and characterized the resulting tumors. Results: Interestingly, the dominant phenotype in these mice was the development of both non-invasive and invasive urothelial carcinomas (9% and 20% respectively, average age of onset 10-12 months of age). Histologically, these tumors were indistinguishable from human urothelial carcinomas. Gene expression profiling of invasive tumors derived from ATDC tg mice demonstrated a marked overlap with gene signatures of human invasive bladder cancers. ATDC was the 11th most highly up-regulated gene in bladder cancers represented in the Oncomine gene expression database. Analysis of a human bladder cancer tissue microarray (311 samples) by IHC showed elevated expression in 70% (173/252) of muscle-invasive carcinomas, 22% (5/23) of papillary tumors and little or no expression in normal bladder urothelium. ATDC tg mouse bladder tumors demonstrated loss of p53 signaling and down-regulation of PTEN expression, which correlated with ATDC induced methylation of the PTEN promoter by DNMT3A. Furthermore, ATDC knock-down in invasive cancer cell lines resulted in decreased proliferation, invasion and reactivation of p53-mediated signaling and PTEN expression. Conclusions: ATDC is a novel oncogene that is highly expressed in human bladder cancers and is sufficient to drive the development of invasive bladder tumors in tg mice. The mechanism by which ATDC drives bladder cancer formation involves alterations in p53 and PTEN pathways known to be important in bladder tumorigenesis.

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