A Molecular Signature in Superficial Bladder Carcinoma Predicts Clinical Outcome

• Published in: Clinical cancer research Vol. 11; no. 11; pp. 4029 - 4036
• Main Authors: DYRSKJØT, Lars, ZIEGER, Karsten, KRUHØFFER, Mogens, THYKJAER, Thomas, JENSEN, Jens L, PRIMDAHL, Hanne, AZIZ, Natasha, MARCUSSEN, Niels, MØLLER, Klaus, ØRNTOFT, Torben F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-06-2005
• Subjects: Antineoplastic agents; Biological and medical sciences; classification; Cluster Analysis; diagnosis; Disease Progression; Expressed Sequence Tags; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - genetics; Genome, Human; Humans; Medical sciences; microarray; Neoplasm Invasiveness - genetics; Neoplasm Staging; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis - methods; Pharmacology. Drug treatments; Prognosis; Tumors of the urinary system; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urinary system disease; Prognosis; Bladder disease; Malignant tumor; Urinary tract disease; Bladder carcinoma; Predictive factor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2095

Purpose: Cancer of the urinary bladder is a common malignant disease in the western countries. The majority of patients presents with
superficial tumors with a high recurrence frequency, a minor fraction of these patients experience disease progression to
a muscle invasive stage. No clinical useful molecular markers exist to identify patients showing later disease progression.
The purpose of this study was to identify markers of disease progression using full-genome expression analysis.
Experimental Design: We did a full-genome expression analysis (59,619 genes and expressed sequence tags) of superficial bladder tumors from 29
bladder cancer patients (13 without later disease progression and 16 with later disease progression) using high-density oligonucleotide
microarrays. We used supervised learning for identification of the optimal genes for predicting disease progression. The identified
genes were validated on an independent test set (74 superficial tumor samples) using in house-fabricated 60-mer oligonucleotide
microarrays.
Results: We identified a 45-gene signature of disease progression. By monitoring this progression signature in an independent test
set, we found a significant correlation between our classifications and the clinical outcome ( P < 0.03). The genes identified as differentially expressed were involved in regulating apoptosis, cell differentiation, and
cell cycle and hence may represent potential therapeutic targets.
Conclusions: Our results indicate that it may be possible to identify patients with a high risk of disease progression at an early stage
using a molecular signature present already in the superficial tumors. In this way, better treatment and follow-up regimens
could be assigned to patients suffering from superficial bladder cancer.