scholarly journals Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

2017 ◽  
Vol 14 (1) ◽  
pp. 1193-1199 ◽  
Author(s):  
Yoshiaki Yamamoto ◽  
Yutaka Suehiro ◽  
Atomu Suzuki ◽  
Ryosuke Nawata ◽  
Yoshihisa Kawai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Copy Number ◽  
Prognostic Markers ◽  
Copy Number Variations ◽  
Invasive Bladder Cancer ◽  
Dna Copy Number ◽  
Muscle Invasive Bladder Cancer ◽  
Dna Copy Number Variations ◽  
Muscle Invasive

FGFR3 mutations, but not FGFR3 expression and FGFR3 copy-number variations, are associated with favourable non-muscle invasive bladder cancer

2014 ◽  
Vol 465 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Yann Neuzillet ◽  
Bas W. G. van Rhijn ◽  
Nadia L. Prigoda ◽  
Bharati Bapat ◽  
Liyang Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Copy Number ◽  
Copy Number Variations ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Fgfr3 Mutations

scholarly journals Copy Number Variations of CEP63, FOSL2 and PAQR6 Serve as Novel Signatures for the Prognosis of Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhao Cai ◽  
Huang Chen ◽  
Jingqiao Bai ◽  
Yang Zheng ◽  
Jianhui Ma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factors ◽  
High Risk ◽  
Copy Number ◽  
Copy Number Variations ◽  
Invasive Bladder Cancer ◽  
Gene Copy ◽  
Muscle Invasive Bladder Cancer ◽  
Copy Numbers ◽  
Muscle Invasive

BackgroundFinding effective prognostic signatures is of great urgency due to the high risk of recurrence and progression of bladder cancer (BC). Although a lot of genetic alterations are involved in the carcinogenesis, none of them were referred in the current risk group stratifications. In this study, we aimed to find significant copy number variations (CNVs) to predict prognosis for BC patients.MethodsCNVs with high aberration frequencies in BC were explored by array-based comparative genomic hybridization in 65 tumor samples. Candidates were validated in independent groups of BC tumor samples (n=219) and urine samples (n=123). 3D digital PCR was applied for detecting accurate gene copy numbers in BC urine. In order to explore the prognostic value of candidate CNVs, all enrolled patients were followed up for the disease-free survival (DFS). Cox proportional hazards regression analysis was performed to find the independent prognostic factors for DFS.ResultsCNVs of CEP63, FOSL2 and PAQR6 with high aberration frequencies (67.7%, 56.9% and 60.0%, respectively) were found in BC tumors. Copy numbers of CEP63, FOSL2 and PAQR6 were gained in 219 tumor samples. CNVs of CEP63 and FOSL2 were correlated with advanced tumor stage and high grade. Retrospective analysis (median follow-up time: 69 months) revealed that CNVs of CEP63 and FOSL2 were independent prognostic factors for DFS of non-muscle-invasive bladder cancer (NMIBC) patients, while CNVs of FOSL2 and PAQR6 were independent prognostic factors for DFS of muscle-invasive bladder cancer (MIBC) patients. Models for predicting DFS were constructed based on CNVs of three genes. Patients with high prognostic indexes tended to have poor DFS. Prognostic index can also help to identify those with worse outcomes among high risk NMIBC patients. Copy number gains of CEP63 and FOSL2 in urine were found to be significantly correlated with poor DFS of NMIBC patients.ConclusionsCNVs of CEP63, FOSL2 and PAQR6 were capable of predicting DFS and may serve as promising signatures for prognosis of BC.

scholarly journals FAM70Bas a Novel Prognostic Marker for Cancer Progression and Cancer-Specific Death in Muscle-Invasive Bladder Cancer

2012 ◽  
Vol 53 (9) ◽  
pp. 598 ◽  
Author(s):  
Ho-Won Kang ◽  
Hyung-Yoon Yoon ◽  
Yun-Sok Ha ◽  
Won Tae Kim ◽  
Yong-June Kim ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Marker ◽  
Cancer Progression ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Fatty acid synthase, Her2/neu, and E2F1 as prognostic markers of progression in non-muscle invasive bladder cancer

2019 ◽  
Vol 39 ◽  
pp. 42-52 ◽  
Author(s):  
Aziza E. Abdelrahman ◽  
Hayam E. Rashed ◽  
Ehab Elkady ◽  
Eman A. Elsebai ◽  
Ahmed El-Azony ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Prognostic Markers ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Down-regulation of A-FABP predicts non-muscle invasive bladder cancer progression: investigation with a long term clinical follow-up

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Christel Mathis ◽  
Isabelle Lascombe ◽  
Franck Monnien ◽  
Hugues Bittard ◽  
François Kleinclauss ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Invasive Bladder Cancer ◽  
Down Regulation ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Prognostic markers in muscle invasive bladder cancer

2002 ◽  
Vol 20 (3) ◽  
pp. 190-195 ◽  
Author(s):  
Rabi Tiguert ◽  
Annie Lessard ◽  
Alan So ◽  
Yves Fradet
Keyword(s):  
Bladder Cancer ◽  
Prognostic Markers ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Development of a genomic-clinical classifier for predicting progression after radical cystectomy in patients with muscle invasive bladder cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4542-4542
Author(s):  
Anirban Pradip Mitra ◽  
Nicholas Erho ◽  
Lucia L.C. Lam ◽  
Ismael A. Vergara ◽  
Thomas Sierocinski ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Cancer Progression ◽  
External Validation ◽  
Multivariable Analysis ◽  
Invasive Bladder Cancer ◽  
K Nearest Neighbor ◽  
Muscle Invasive Bladder Cancer ◽  
Validation Set ◽  
Muscle Invasive

4542 Background: The mainstay of muscle-invasive bladder cancer treatment is surgical resection with/without multi-agent chemotherapy. Management decisions are based on a small number of clinical and pathologic parameters with poor prognostic and predictive power. There is an urgent need for enhanced biomarkers to guide therapy of this lethal disease. Here we have developed a genomic signature of bladder cancer progression using whole transcriptome profiling technology. Methods: 251 FFPE bladder cancer specimens were obtained from patients undergoing radical cystectomy at the University of Southern California (1998-2004). All patients had pT2-T4a,N0 urothelial carcinoma in the absence of pre-operative chemotherapy. Median follow-up was 5 years. RNA expression levels were measured with 1.4 million feature oligonucleotide microarrays. Patients were divided into a training set (2/3 of cohort) to develop a genomic classifier for risk of progression (defined as any type of bladder cancer recurrence), and a validation set (1/3 of cohort). In parallel, multivariable analysis was used to develop a clinical classifier using typical clinical and pathologic variables. Finally, a genomic-clinical classifier was built combining the genomic classifier with clinical variables using logistic regression. The receiver-operator characteristic (ROC) area under the curve (AUC) metric was used to evaluate each classifier in the validation set. Results: The genomic classifier consisted of 89 features corresponding to 80 genes that were combined in a k-nearest neighbor model (KNN89). KNN89 showed an AUC of 0.77 in ROC analysis on the validation set. The best clinical classifier showed an AUC of 0.72. The genomic-clinical classifier demonstrated an AUC of 0.81. Multivariable analysis incorporating all clinical parameters and KNN89 further revealed that KNN89 was the only significant predictor of bladder cancer progression (p=0.0077). Conclusions: We have developed a combined genomic-clinical classifier that shows improved performance over clinical models alone for prediction of progression after radical cystectomy. External validation of this classifier is ongoing.

A genome-wide query of somatic copy number alterations to predict lymph node metastases and survival in patients with muscle-invasive bladder cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 325-325
Author(s):  
Karla Lindquist ◽  
Thomas Sanford ◽  
Terence W. Friedlander ◽  
Pamela Paris ◽  
Sima P. Porten
Keyword(s):  
Bladder Cancer ◽  
Copy Number ◽  
Treatment Decisions ◽  
Invasive Bladder Cancer ◽  
Copy Number Alterations ◽  
Muscle Invasive Bladder Cancer ◽  
Genome Wide ◽  
A Genome ◽  
Muscle Invasive ◽  
One Year

325 Background: Patients with muscle-invasive bladder cancer (MIBC) have a poor prognosis if the cancer has metastasized to surrounding lymph nodes (LN). Adding tumor-based genomic tests that improve prediction of LN status and prognosis over clinical variables alone would be useful to clinicians in making treatment decisions, potentially improving outcomes for these patients. Methods: We performed a genome-wide query of copy number alterations (CNAs) in MIBC tumors from 237 patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy ( ≥ 10 nodes) without neoadjuvant treatment. We independently analyzed pathology reports and copy number data to confirm LN status and gene-level CNAs. Using elastic net and logistic regression models, we sought to identify a set of genes with CNAs that predict LN status. We also tested for association between CNAs and survival. Results: We identified 26 genes with CNAs that predicted LN status. Those located on chr3p25 and chr11p11 had gains associated with LN positivity after adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined (p = 0.03). CNAs at these loci were also associated with one-year survival in the cohort overall (p < 0.01), as well as in LN-positive patients after adjusting for node stage, LN density, and extracapsular extension (p < 0.01). Conclusions: We have identified a small set of genes with CNAs in MIBC tumors that robustly predict LN status and one-year survival. A simple copy number-based test based on these genes could potentially improve preoperative LN status determination and help inform adjuvant treatment decisions to improve outcomes in MIBC patients.

Germline DNA copy number polymorphism to predict the efficacy of BCG therapy for non-muscle invasive bladder cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 431-431
Author(s):  
Yoshiaki Yamamoto ◽  
Sho Ozawa ◽  
Masahiro Samoto ◽  
Junichi Mori ◽  
Ryo Inoue ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Copy Number ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Intravesical Instillation ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Bcg Therapy ◽  
Muscle Invasive

431 Background: Bacillus Calmette-Guerin (BCG) intravesical instillation is the most effective immunotherapy for non-muscle-invasive bladder cancer (NMIBC), however there are few reliable markers to elucidate the efficacy of BCG therapy. Germline copy number polymorphisms (CNPs) are expected to affect various diseases including human malignancies, but the significance of CNPs in NMIBC treated with BCG therapy remains unclear. FAM81A located on 15q22.2 was reported as one of tumor-associated ETS shared target genes in prostate cancer. PCSK6 located on 15q26.3 was reported to regulate proliferation and tumor progression in several cancers. The purpose of this study is to determine the prognostic value of CNPs for NMIBC treated with BCG therapy. To our knowledge, this is the first report to confirm CNPs as a potential biomarker for assessing the efficacy of immunotherapy. Methods: Array comparative genomic hybridization (CGH) was performed to search for candidate whole genome-wide CNPs related to NMIBC susceptibility. Next, quantitative real-time polymerase chain reaction was carried out to evaluate the effect of BCG therapy for 57 Japanese patients with NMIBC treated with BCG intravesical instillation. Results: Eleven CNPs were associated with NMIBC risk in array CGH. FAM81A and PCSK6 copy number according to those CNPs examined showed significant relationship with disease progression in NMIBC treated with BCG. The means of the relative copy numbers of patients with CNP and those without it were 1.58 and 2.10 for FAM81A ( P < 0.0001), and 1.06 and 1.80 for PCSK6 ( P < 0.0001), respectively. Univariate Cox proportional hazards regression analysis showed that FAM81A ( P = 0.0022), and PCSK6 ( P = 0.0147) copy number had a significant effect on progression-free survival. In multivariate analyses, FAM81A copy number was an independent prognostic factor for progression-free survival ( P = 0.0419, RR = 7.59, 95% CI, 1.07–153.42). The combination of FAM81A or PCSK6 CNP was the most significant prognostic biomarker to predict the efficacy of BCG therapy for NMIBC ( P = 0.0002). Conclusions: Germline DNA CNPs may be a potential new biomarker for estimating the efficacy of BCG therapy in Japanese patients with NMIBC.

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