Unknown,Transcriptomics,Genomics,Proteomics

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Discovery and validation of a novel expression signature for recurrence in high-risk bladder cancer post-cystectomy

ABSTRACT: Purpose: Selecting muscle-invasive bladder cancer patients for adjuvant therapy is currently based on clinical variables with limited power. We hypothesized that genomic-based signatures can outperform clinical models to identify patients at higher risk. Method:Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. A cohort comprised of 225 patients with organ-confined, muscle-invasive (pT2N0M0),extravesical (pT3-4aN0M0), and node-positive (pTanyN1-3M0) UCB who underwent radicalcystectomy at the University of Southern California between 1998 and 2004 was used. Each patient had aminimum two-year follow-up post-cystectomy unless they recurred prior to that date. Patients receiving neoadjuvant chemotherapy, and those with clinical evidence of lymphadenopathy or distant metastasis at diagnosis were excluded.

ORGANISM(S): Homo sapiens

SUBMITTER: Mohammed Alshalalfa

PROVIDER: E-GEOD-57933 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.

Mitra Anirban P AP Lam Lucia L LL Ghadessi Mercedeh M Erho Nicholas N Vergara Ismael A IA Alshalalfa Mohammed M Buerki Christine C Haddad Zaid Z Sierocinski Thomas T Triche Timothy J TJ Skinner Eila C EC Davicioni Elai E Daneshmand Siamak S Black Peter C PC

Journal of the National Cancer Institute 20141024 11

<h4>Background</h4>Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone.<h4>Methods</h4>Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival ...[more]

PMID: 25344601

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Project description:This study aimed to identify the genetic signatures associated with disease prognosis in bladder cancer. We used 165 primary bladder cancer samples, 23 recurrent non-muscle invasive tumor tissues, 58 normal looking bladder mucosae surrounding cancer and 10 normal bladder mucosae for microarray analysis. Hierarchical clustering was used to stratify the prognosis-related gene classifiers. For validation, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of top-ranked 14 genes was performed. On unsupervised hierarchical clustering using prognosis related gene-classifier, tumors were divided into 2 groups. The high risk gene signatures had significantly poor prognosis compared to low risk gene signatures (P<0.001 by the log-rank test, respectively). The prognosis-related gene classifiers correlated significantly with recurrence of non-muscle invasive bladder cancer (hazard ratio, 4.09; 95% confidence interval [CI], 1.94 to 8.64; P<0.001), and progression (hazard ratio, 23.68; 95% confidence interval [CI], 4.91 to 114.30; P<0.001), cancer-specific survival (hazard ratio, 29.25; 95% confidence interval [CI], 3.47 to 246.98; P=0.002) and overall survival (hazard ratio, 23.33; 95% confidence interval [CI], 4.97 to 109.50; P<0.001) of muscle invasive bladder cancer (p < 0.001, respectively). No patient with non-muscle invasive bladder cancer experienced cancer progression in low risk gene signature group. Prognosis-related gene classifiers validated by RT- PCR showed identical results. Prognosis related gene-classifiers provided strong predictive value for disease outcome. These gene classifiers could assist in selecting patients who might benefit from more aggressive therapeutic intervention or surveillance. Keywords: Gene expression, Bladder cancer, Prognosis 165 primary bladder cancer samples and 23 recurrent non-muscle invasive tumor tissues from 14 patients were taken in the Chungbuk National University Hospital. Only histologically verified transitional cell carcinoma samples were selected. Simultaneously 58 normal looking bladder mucosae surrounding cancer were obtained during the operation, which were histologically confirmed normal. Also, 10 normal bladder mucosae were obtained from patients with benign disease. The normal controls were determined to be free of cancer after revealing no malignant cells on urine cytology and no observable bladder cancer on cystoscopic examination during operation for their diseases, and were histologically reconfirmed normal.

Dataset Information

Discovery and validation of a novel expression signature for recurrence in high-risk bladder cancer post-cystectomy

Publications

Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.

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