Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human advanced bladder cancer to predict response and survival following chemotherapy in patients


ABSTRACT: BACKGROUND; Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS; Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS; Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION; Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Experiment Overall Design: Tumors from 30 patients with advanced bladder cancer used in the study. A SAM analysis was used for identifying genes co-varying with treatment response.

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Dyrskjøt Andersen 

PROVIDER: E-GEOD-5287 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer.

Als Anne B AB   Dyrskjøt Lars L   von der Maase Hans H   Koed Karen K   Mansilla Francisco F   Toldbod Helle E HE   Jensen Jens L JL   Ulhøi Benedicte P BP   Sengeløv Lisa L   Jensen Klaus M E KM   Orntoft Torben F TF  

Clinical cancer research : an official journal of the American Association for Cancer Research 20070801 15 Pt 1


<h4>Purpose</h4>Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response and survival.<h4>Experimental design</h4>Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to s  ...[more]

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