c105 molecular subtyping of bladder cancer using kohonen self-organizing maps

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C105 Molecular subtyping of bladder cancer using Kohonen self-organizing maps Eur Urol Suppl 2013;12;e1213 Borkowska E.M. 1 , Kruk A. 2 , Jedrzejczyk A. 3 , Rozniecki M. 4 , Jablonowski Z. 5 , Traczyk M. 1 , Constantinou M. 1 , Banaszkiewicz M. 1 , Pietrusinski M. 1 , Sosnowski M. 5 , Hamdy F.C. 6 , Peter S. 7 , Catto J.W.F. 7 , Kaluzewski B. 1 1 Medical University of Lodz, Dept. of Clinical and Laboratory Genetics, Lodz, Poland, 2 University of Lodz, Dept. of Ecology and Vertebrate Zoology, Lodz, Poland, 3 John Paul II Memorial Regional Hospital In Bełchatow, Dept. of Urology, Belchatow, Poland, 4 NZOZ Urological Doctors, Marek Rozniecki and Partners, Dept. of Urology, Lask, Poland, 5 Medical University of Lodz, Dept. of Urology I Clinic, Lodz, Poland, 6 University of Oxford, Dept. of Surgical Sciences, Oxford, United Kingdom, 7 Institute For Cancer Studies and Academic Urology Unit University of Sheffield, Dept. of Urology, Sheffield, United Kingdom INTRODUCTION & OBJECTIVES: Kohonen self-organizing maps (KNN SOMs) are unsupervised Artificial Neural Networks (ANN) that are good for low density data visualisation. They easily deal with complex and non-linear relationships between variables. MATERIAL & METHODS: We evaluated molecular events that characterize high and low grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with SOM to stratify tumours according to the risk of progression to more advanced disease. RESULTS: In univariable analysis, tumor stage (log rank p=0.006) and grade (p<0.001), HPV DNA (p<0.004), Chromosome 9 loss (p=0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (p=0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, p=0.001, OR.2.9 (95% CI 1.6-5.2)) and the presence of HPV DNA (p=0.017, OR 3.8 (95% CI 1.3-11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank p=0.39). These genetic variables were presented to KNN SOM input neurons. CONCLUSIONS: KNN SOMs are suitable for complex data integration, allow easy visualization of outcomes and may stratify BC progression more robustly than hierarchical clustering.

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Page 1: C105 Molecular subtyping of bladder cancer using Kohonen self-organizing maps

C105 Molecular subtyping of bladder cancer using Kohonen self-organizing maps Eur Urol Suppl 2013;12;e1213

Borkowska E.M.1, Kruk A.2, Jedrzejczyk A.3, Rozniecki M.4, Jablonowski Z.5, Traczyk M.1, Constantinou M.1, Banaszkiewicz

M.1, Pietrusinski M.1, Sosnowski M.5, Hamdy F.C.6, Peter S.7, Catto J.W.F.7, Kaluzewski B.1

1Medical University of Lodz, Dept. of Clinical and Laboratory Genetics, Lodz, Poland, 2University of Lodz, Dept. of Ecology and

Vertebrate Zoology, Lodz, Poland, 3John Paul II Memorial Regional Hospital In Bełchatow, Dept. of Urology, Belchatow, Poland, 4NZOZ Urological Doctors, “Marek Rozniecki and Partners”, Dept. of Urology, Lask, Poland, 5Medical University of Lodz, Dept.

of Urology I Clinic, Lodz, Poland, 6University of Oxford, Dept. of Surgical Sciences, Oxford, United Kingdom, 7Institute For Cancer Studies and Academic Urology Unit University of Sheffield, Dept. of Urology, Sheffield, United Kingdom

INTRODUCTION & OBJECTIVES: Kohonen self-organizing maps (KNN SOMs) are unsupervised Artificial Neural

Networks (ANN) that are good for low density data visualisation. They easily deal with complex and non-linear relationships

between variables.

MATERIAL & METHODS: We evaluated molecular events that characterize high and low grade BC pathways in the tumors

from 104 patients. We compared the ability of statistical clustering with SOM to stratify tumours according to the risk of

progression to more advanced disease.

RESULTS: In univariable analysis, tumor stage (log rank p=0.006) and grade (p<0.001), HPV DNA (p<0.004), Chromosome 9

loss (p=0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (p=0.02) were associated with progression. Multivariable

analysis of these parameters identified that tumor grade (Cox regression, p=0.001, OR.2.9 (95% CI 1.6-5.2)) and the presence

of HPV DNA (p=0.017, OR 3.8 (95% CI 1.3-11.4)) were the only independent predictors of progression. Unsupervised

hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log

rank p=0.39). These genetic variables were presented to KNN SOM input neurons.

CONCLUSIONS: KNN SOMs are suitable for complex data integration, allow easy visualization of outcomes and may stratify

BC progression more robustly than hierarchical clustering.