scholarly journals Prognostic Significance of Lymphocyte Infiltration and a Stromal Immunostaining of a Bladder Cancer Associated Diagnostic Panel in Urothelial Carcinoma

Diagnostics ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 14
Author(s):  
Hideki Furuya ◽  
Owen T.M. Chan ◽  
Kanani Hokutan ◽  
Yutaro Tsukikawa ◽  
Keanu Chee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Immunohistochemical Staining ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Secreted Proteins ◽  
Bladder Tumors ◽  
Stromal Component ◽  
Diagnostic Signature ◽  
Diagnostic Panel

We set out to expand on our previous work in which we reported the epithelial expression pattern of a urine-based bladder cancer-associated diagnostic panel (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1, and VEGFA). Since many of the analytes in the bladder cancer-associated diagnostic signature were chemokines, cytokines, or secreted proteins, we set out to report the stromal staining pattern of the diagnostic signature as well as CD3+ (T-cell) cell and CD68+ (macrophage) cell staining in human bladder tumors as a snapshot of the tumor immune landscape. Immunohistochemical staining was performed on 213 tumor specimens and 74 benign controls. Images were digitally captured and quantitated using Aperio (Vista, CA). The expression patterns were correlated with tumor grade, tumor stage, and outcome measures. We noted a positive correlation of seven of the 10 proteins (excluding A1AT and IL8 which had a negative association and VEGFA had no association) in bladder cancer. The overexpression of MMP10 was associated with higher grade disease, while overexpression of MMP10, PAI1, SDC1 and ANG were associated with high stage bladder cancer and CA9 was associated with low stage bladder cancer. Increased tumor infiltration of CD68+ cells were associated with higher stage disease. Overall survival was significantly reduced in bladder cancer patients’ whose tumors expressed eight or more of the 10 proteins that comprise the bladder cancer diagnostic panel. These findings confirm that the chemokines, cytokines, and secreted proteins in a urine-based diagnostic panel are atypically expressed, not only in the epithelial component of bladder tumors, but also in the stromal component of bladder tumors and portends a worse overall survival. Thus, when assessing immunohistochemical staining, it is important to report staining patterns within the stroma as well as the entire stroma itself.

scholarly journals IMPDH2 and HPRT expression and a prognostic significance in preoperative and postoperative patients with osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Parunya Chaiyawat ◽  
Areerak Phanphaisarn ◽  
Nutnicha Sirikaew ◽  
Jeerawan Klangjorhor ◽  
Viraporn Thepbundit ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Drug Repurposing ◽  
Survival Times ◽  
Metabolizing Enzymes ◽  
Hypoxanthine Guanine Phosphoribosyltransferase ◽  
High Grade Osteosarcoma ◽  
Enneking Stage

AbstractOsteosarcoma is one of the most aggressive bone tumors in children and adolescents. Development of effective therapeutic options is still lacking due to the complexity of the genomic background. In previous work, we applied a proteomics-guided drug repurposing to explore potential treatments for osteosarcoma. Our follow-up study revealed an FDA-approved immunosuppressant drug, mycophenolate mofetil (MMF) targeting inosine-5′-phosphate dehydrogenase (IMPDH) enzymes, has an anti-tumor effect that appeared promising for further investigation and clinical trials. Profiling of IMPDH2 and hypoxanthine–guanine phosphoribosyltransferase (HPRT), key purine-metabolizing enzymes, could deepen understanding of the importance of purine metabolism in osteosarcoma and provide evidence for expanded use of MMF in the clinic. In the present study, we investigated levels of IMPDH2, and HPRT in biopsy of 127 cases and post-chemotherapy tissues in 20 cases of high-grade osteosarcoma patients using immunohistochemical (IHC) analysis. Cox regression analyses were performed to determine prognostic significance of all enzymes. The results indicated that low levels of HPRT were significantly associated with a high Enneking stage (P = 0.023) and metastatic status (P = 0.024). Univariate and multivariate analyses revealed that patients with low HPRT expression have shorter overall survival times [HR 1.70 (1.01–2.84), P = 0.044]. Furthermore, high IMPDH2/HPRT ratios were similarly associated with shorter overall survival times [HR 1.67 (1.02–2.72), P = 0.039]. Levels of the enzymes were also examined in post-chemotherapy tissues. The results showed that high IMPDH2 expression was associated with shorter metastasis-free survival [HR 7.42 (1.22–45.06), P = 0.030]. These results suggest a prognostic value of expression patterns of purine-metabolizing enzymes for the pre- and post-chemotherapy period of osteosarcoma treatment.

scholarly journals Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hye Min Kim ◽  
Yu Kyung Lee ◽  
Ja Seung Koo
Keyword(s):  
Overall Survival ◽  
Immunohistochemical Staining ◽  
Univariate Analysis ◽  
Phyllodes Tumor ◽  
Tissue Microarrays ◽  
Histologic Grade ◽  
Cancer Associated Fibroblast ◽  
Stromal Component ◽  
Clinicopathologic Parameters ◽  
Related Proteins

Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT).Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFRα/β, and NG2) and analyzed the results according to clinicopathologic parameters.Results. Expression of PDGFRαand PDGFRβin the stromal component increased with increasing histologic grade of PT (p=0.003andp=0.034, resp.). Among clinicopathologic parameters, only expression of FAPαin stroma was associated with distant metastasis (p=0.002). In univariate analysis, stromal expression of PDGFRαwas associated with shorter overall survival (p=0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRαstromal positivity were associated with shorter overall survival (p=0.006andp=0.050, resp.). Furthermore, expression of PDGFRβin stroma was associated with shorter overall survival in patients with malignant PT (p=0.041).Conclusion. Stromal expression of PDGFRαand PDGFRβincreased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.

Defining Molecular Profiles of Poor Outcome in Patients With Invasive Bladder Cancer Using Oligonucleotide Microarrays

2006 ◽  
Vol 24 (5) ◽  
pp. 778-789 ◽  
Author(s):  
Marta Sanchez-Carbayo ◽  
Nicholas D. Socci ◽  
Juanjo Lozano ◽  
Fabien Saint ◽  
Carlos Cordon-Cardo
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Outcome ◽  
Tumor Staging ◽  
Invasive Disease ◽  
Bladder Tumors ◽  
Tissue Arrays ◽  
Node Metastases ◽  
Normal Urothelium ◽  
Immunohistochemical Analyses

Purpose Bladder cancer is a common malignancy characterized by a poor clinical outcome when tumors progress into invasive disease. We sought to define genetic signatures characteristic of aggressive clinical behavior in advanced bladder tumors. Methods Oligonucleotide arrays were utilized to analyze the transcript profiles of 105 bladder tumors: 33 superficial, 72 invasive lesions, and 52 normal urothelium. Hierarchical clustering and supervised algorithms were used to classify and stratify bladder tumors on the basis of stage, node metastases, and overall survival. Immunohistochemical analyses on bladder cancer tissue arrays (n = 294 cases) served to validate associations between marker expression, staging and outcome. Results Hierarchical clustering classified normal urothelium, superficial, and invasive tumors with 82.2% accuracy, and stratified bladder tumors on the basis of clinical outcome. Predictive algorithms rendered an 89%-correct rate for tumor staging using genes differentially expressed between superficial and invasive tumors. Accuracies of 82% and 90% were obtained for predicting overall survival when considering all patients with bladder cancer or only patients with invasive disease, respectively. A genetic profile consisting of 174 probes was identified in those patients with positive lymph nodes and poor survival. Two independent Global Test runs confirmed the robust association of this profile with lymph node metastases (P = 7.3–13) and overall survival (P = 1.9–14) simultaneously. Immunohistochemical analyses on tissue arrays sustained the significant association of synuclein with tumor staging and clinical outcome (P = .002). Conclusion Gene profiling provides a genomic-based classification scheme of diagnostic and prognostic utility for stratifying advanced bladder cancer. Identification of this poor outcome profile could assist in selecting patients who may benefit from more aggressive therapeutic intervention.

scholarly journals Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Shitong Lin ◽  
Canhui Cao ◽  
Yifan Meng ◽  
Ping Wu ◽  
Peipei Gao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Invasive Carcinoma ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Functional Enrichment ◽  
Clinicopathological Parameters ◽  
Genetic Mutations ◽  
Study Results ◽  
Rab Family ◽  
Potential Biomarkers

Abstract Purpose: Several RAB family genes have been studied extensively and proven to play pivotal roles in the occurrence and development of certain cancers. Here, we explored commonly expressed RAB family genes in humans and their prognostic significance using bioinformatics, and then identified potential biomarkers of breast invasive carcinoma (BRCA). Materials and methods: The prognostic values (overall survival) of RAB family genes in BRCA were obtained using Gene Expression Profiling Interactive Analysis (GEPIA). The expression patterns of RAB family genes and their relationships with clinicopathological parameters in BRCA were measured using the ONCOMINE and UALCAN databases, respectively. Genetic mutations and survival analysis were investigated using the cBio Cancer Genomics Portal (c-BioPortal). Interacting genes of potential biomarkers were identified using STRING, and functional enrichment analyses were performed using FunRich v3.1.3. Results: In total, 64 RAB genes were identified and analyzed in our study. Results showed that RAB1B, RAB2A, and RAB18 were up-regulated and significantly associated with poor overall survival in BRCA. Furthermore, their higher expression was positively correlated with clinicopathological parameters (e.g. cancer stage and nodal metastasis status). DNA copy number amplifications and mRNA up-regulation were the main genetic mutations, and the altered group showed significantly poorer overall survival compared with the unaltered group. Functional enrichment analysis of RAB1B, RAB2A, and RAB18 indicated they were closely involved in GTPase activity. Conclusions:RAB1B, RAB2A, and RAB18 were up-regulated and significantly correlated with poor prognosis in BRCA. Thus, they could be applied as novel biomarkers of BRCA in future studies.

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.

scholarly journals Fascin Inhibitors Decrease Cell Migration and Adhesion While Increase Overall Survival of Mice Bearing Bladder Cancers

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2698
Author(s):  
Zhankui Zhao ◽  
Yufeng Wang ◽  
J. Jillian Zhang ◽  
Xin-Yun Huang
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Stage ◽  
Primary Tumor Growth ◽  
Bladder Tumors ◽  
Bladder Cancer Cells ◽  
New Treatment ◽  
New Treatments

Bladder cancer is one of the most common cancers in the world. Early stage bladder tumors can be surgically removed, but these patients usually have relapses. When bladder cancer becomes metastatic, survival is very low. There is an urgent need for new treatments for metastatic bladder cancers. Here, we report that a new fascin inhibitor decreases the migration and adhesion of bladder cancer cells. Furthermore, this inhibitor decreases the primary tumor growth and increases the overall survival of mice bearing bladder cancers, alone, as well as in combination with the chemotherapy medication, cisplatin, or the immune checkpoint inhibitor, anti-PD-1 antibody. These data suggest that fascin inhibitors can be explored as a new treatment for bladder cancers.

Prognostic significance of history of nonmuscle invasive bladder cancer in patients with muscle invasive bladder cancer treated with neoadjuvant chemotherapy followed by surgery.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 375-375
Author(s):  
Yongjune Lee ◽  
Young Seok Kim ◽  
Bumsik Hong ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
History Of ◽  
Muscle Invasive

375 Background: Efficacy of cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for T2-4aN1M0 muscle-invasive bladder cancer (MIBC) was proved by randomize controlled trials. Recent retrospective studies suggested that MIBC patients who had a history of non-muscle invasive bladder cancer (NMIBC) had lower pathologic complete response and worse overall survival rate to NAC and RC. This study aimed to compare clinical outcomes between MIBC that progressed from NMIBC (secondary MIBC) and primary MIBC. Methods: A retrospective analysis of patients with urothelial carcinoma (cT2-4aN0-1M0) who received neoadjuvant chemotherapy from January 2011 and December 2017 in Asan Medical Center was conducted. Clinicopathologic outcomes were compared between 187 patients with primary MIBC and 38 patients with secondary MIBC. Results: Baseline characteristics are well balanced between the groups. Downstaging rate ( < ypT2 and no N upstaging) are 46.7% for secondary MIBC group, 55.6% for primary MIBC group (p = 0.390), and positive pathologic metastatic nodes (ypN1+) are observed in 23.3% for secondary MIBC group, 18.3% for primary MIBC group (p = 0.523). There were no differences in overall survival (OS) (3 year OS 69.3% for secondary MIBC, 70.3% for primary MIBC, p = 0.420), disease-free survival (DFS) (3 year DFS 57.7% vs 56.6%, p = 0.880) between the groups. History of NMIBC is not independent prognostic factor for OS on multivariable analysis. Conclusions: Patients with secondary MIBC treated with NAC showed no differences in NAC response, pathologic downstaging rate, OS, DFS compared to patients with primary MIBC. Prospective or larger cohort study are required in the future. Genomic analysis is ongoing to identify genetic differences between two groups.

scholarly journals Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

2020 ◽  
Author(s):  
Changgang Guo ◽  
Ting Shao ◽  
Dadong Wei ◽  
Zhanhua Wang ◽  
Mingyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Survival Analysis ◽  
Roc Curve ◽  
Prognostic Model ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Prognostic Significance ◽  
Training Group ◽  
Testing Group

Abstract Background Alterations in RNA-binding proteins (RBPs) are reported in various cancer types; however, the role of RBPs in bladder urothelial cancer (BLCA) remains unknown. This study aimed to systematically examine the function and prognostic significance of RBPs in bladder cancer using bioinformatics analyses. Methods RNA sequencing and clinical data for BLCA were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed RBPs (DERBPs) between normal and cancer tissues were identified. Protein-protein interaction (PPI) network of DERBPs was established, and enrichment analysis and visualizations were performed. A total of 404 patients with BLCA from TCGA database were randomly divided into training and testing groups. A prognostic model was constructed using the data from training group, and validated in the testing group. Receiver operating characteristic (ROC) curve and survival analysis were performed to explore the prognostic value of the model. A nomogram was established to predict survival in bladder cancer patients. Finally, the verification of prognosis-related hub RBP survival analysis were performed. Results A total of 388 DERBPs were identified, including 219 upregulated and 169 downregulated RBPs. All RBPs were screened for prognostic model establishment and 9 RBPs (TRIM71, YTHDC1, DARS2, XPOT, ZNF106, FTO, IPO7, EFTUD2, and CTU1) were regarded as prognosis-related hub RBPs in BLCA. Further analysis revealed worse overall survival (OS) in the high-risk cohort compared to the model-based low-risk cohort. The area under the ROC curve was 0.752 in the training group and 0.701 in the testing group, which confirms the good prediction ability. A nomogram was established according to nine prognosis-related RBPs, which showed well predicting ability for BLCA. BLCA patients with high DARS2, XPOT, ZNF106, FTO, and IPO7 expression (on the contrary, low YTHDC1 and CTU1 expression) were correlated to poor overall survival. Conclusions The prognosis-related hub RBPs may be involved in oncogenesis, development, and metastasis of BLCA. Our results will be of great significance in revealing the pathogenesis of BLCA, and developing new therapeutic targets and prognostic molecular markers.

Gene Signature of m 6A regulators in Bladder Cancer: Prognostic Significance and Immune Implication

2019 ◽  
Author(s):  
Yuying Zhang ◽  
Baoyi Zhu ◽  
Yi Cai ◽  
Minghui He ◽  
Chonghe Jiang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Significance ◽  
Gene Signature
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