Online citations, reference lists, and bibliographies.
← Back to Search

The Use Of Genetic Programming In The Analysis Of Quantitative Gene Expression Profiles For Identification Of Nodal Status In Bladder Cancer

A. P. Mitra, A. Almal, Ben George, D. Fry, P. Lenehan, V. Pagliarulo, R. Cote, R. Datar, W. Worzel
Published 2006 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
BackgroundPrevious studies on bladder cancer have shown nodal involvement to be an independent indicator of prognosis and survival. This study aimed at developing an objective method for detection of nodal metastasis from molecular profiles of primary urothelial carcinoma tissues.MethodsThe study included primary bladder tumor tissues from 60 patients across different stages and 5 control tissues of normal urothelium. The entire cohort was divided into training and validation sets comprised of node positive and node negative subjects. Quantitative expression profiling was performed for a panel of 70 genes using standardized competitive RT-PCR and the expression values of the training set samples were run through an iterative machine learning process called genetic programming that employed an N-fold cross validation technique to generate classifier rules of limited complexity. These were then used in a voting algorithm to classify the validation set samples into those associated with or without nodal metastasis.ResultsThe generated classifier rules using 70 genes demonstrated 81% accuracy on the validation set when compared to the pathological nodal status. The rules showed a strong predilection for ICAM1, MAP2K6 and KDR resulting in gene expression motifs that cumulatively suggested a pattern ICAM1>MAP2K6>KDR for node positive cases. Additionally, the motifs showed CDK8 to be lower relative to ICAM1, and ANXA5 to be relatively high by itself in node positive tumors. Rules generated using only ICAM1, MAP2K6 and KDR were comparably robust, with a single representative rule producing an accuracy of 90% when used by itself on the validation set, suggesting a crucial role for these genes in nodal metastasis.ConclusionOur study demonstrates the use of standardized quantitative gene expression values from primary bladder tumor tissues as inputs in a genetic programming system to generate classifier rules for determining the nodal status. Our method also suggests the involvement of ICAM1, MAP2K6, KDR, CDK8 and ANXA5 in unique mathematical combinations in the progression towards nodal positivity. Further studies are needed to identify more class-specific signatures and confirm the role of these genes in the evolution of nodal metastasis in bladder cancer.
This paper references
10.2307/2343225
Adaptive Control Processes: A Guided Tour.
E. S. Page (1961)
10.1007/978-3-319-21852-6_3
Chervonenkis: On the uniform convergence of relative frequencies of events to their probabilities
V. Vapnik (1971)
10.1086/321276
Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer.
M. Ritchie (2001)
10.1111/j.1600-0854.2004.00210.x
Annexin–Actin Interactions
M. Hayes (2004)
10.1016/J.BBRC.2004.07.124
Annexins and disease.
M. Hayes (2004)
Spontaneous hematogenous and lymphatic metastasis, but fibrinogen-deficient mice
Js Palumbo (2002)
Cancer Staging Manual 6th edition
Urinary Bladder
10.1158/1078-0432.CCR-04-2297
Detection of Micrometastases in Pelvic Lymph Nodes in Patients Undergoing Radical Cystectomy for Focally Invasive Bladder Cancer by Real-time Reverse Transcriptase-PCR for Cytokeratin 19 and Uroplakin II
T. Kurahashi (2005)
10.1109/TNN.1997.641482
The Nature Of Statistical Learning Theory
V. Cherkassky (1997)
10.1200/JCO.2005.05.516
Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy
Y. Lotan (2005)
10.1038/19783
Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex
C. Rachez (1999)
10.1007/3-540-44795-4_32
Symbolic Discriminant Analysis for Mining Gene Expression Patterns
J. Moore (2001)
Genetic programming - on the programming of computers by means of natural selection
J. Koza (1993)
10.1038/374193A0
A kinase–cyclin pair in the RNA polymerase II holoenzyme
S. Liao (1995)
Tnm independent prognostic factors in lung cancer.
K. Kawamukai (2004)
10.1038/ncpuro0008
Early cystectomy for clinical stage T1 bladder cancer
Brent K Hollenbeck (2004)
10.1165/AJRCMB.19.1.3076
Expression measurement of many genes simultaneously by quantitative RT-PCR using standardized mixtures of competitive templates.
J. Willey (1998)
10.1016/S1097-2765(00)80131-8
NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription.
X. Sun (1998)
10.1016/S1097-2765(00)80254-3
The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergistically with other PCs.
S. Malik (2000)
10.1006/GENO.1994.1201
Organization of the human annexin V (ANX5) gene.
B. Cookson (1994)
10.4049/jimmunol.166.11.6877
The p38 Mitogen-Activated Protein Kinase Mediates Cytoskeletal Remodeling in Pulmonary Microvascular Endothelial Cells Upon Intracellular Adhesion Molecule-1 Ligation1
Q. Wang (2001)
10.2174/1566524033479483
The role of apoptosis in tumor progression and metastasis.
Jason L. Townson (2003)
10.1002/cncr.11940
Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma
F. Esteva (2004)
Schomig A: Tissue factor cytoplasmic domain stimulates migration by activation of the GTPase Rac1 and the mitogen-activated protein kinase
I Ott (2005)
10.1097/S0022-5347(01)68436-2
Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging.
J. Montie (2005)
10.1016/0005-1098(78)90005-5
Modeling By Shortest Data Description*
J. Rissanen (1978)
10.1111/j.1349-7006.2003.tb01514.x
Vascular endothelial growth factor receptor‐2: Its unique signaling and specific ligand, VEGF‐E
M. Shibuya (2003)
10.1161/01.CIR.0000153333.52294.42
Tissue Factor Cytoplasmic Domain Stimulates Migration by Activation of the GTPase Rac1 and the Mitogen-Activated Protein Kinase p38
I. Ott (2005)
Denissenko MF: Role of ICAM1 in invasion of human breast cancer cells
C Rosette (2005)
10.1186/1477-7819-3-43
Extent of lymphadenectomy in radical cystectomy for bladder cancer
M. Ather (2005)
10.1055/S-0037-1613412
Fibrinogen mediates bladder cancer cell migration in an ICAM-1-dependent pathway.
Y. Roche (2003)
10.1023/B:GENP.0000030196.55525.f7
Genetic Programming for Mining DNA Chip Data from Cancer Patients
W. Langdon (2004)
10.1046/J.1432-1327.2000.01525.X
Annexin V relocates to the platelet cytoskeleton upon activation and binds to a specific isoform of actin.
E. Tzima (2000)
10.1109/TPAMI.2005.249
Theoretical bounds of majority voting performance for a binary classification problem
A. Narasimhamurthy (2005)
10.1007/3-540-45103-X_37
A Framework for the Analysis of Majority Voting
M. Narasimhamurthy (2003)
10.2307/2283175
Adaptive Control Processes: A Guided Tour.
M. Freimer (1965)
10.1200/JCO.2001.19.3.666
Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.
J. Stein (2001)
10.1111/j.1464-410X.2005.05557.x
Molecular staging of bladder cancer
A. P. Mitra (2005)
Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis.
T. Belhocine (2002)
10.1128/MMBR.68.2.320-344.2004
ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions
Philippe P Roux (2004)
10.1148/RADIOL.2332031111
Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging.
W. Deserno (2004)
AF: The role of apoptosis in tumor progression and metastasis
JL Townson (2003)
Role of ICAM 1 in invasion of human breast cancer cells
C Rosette (2005)
10.1128/MCB.21.14.4604-4613.2001
Characterization of Mediator Complexes from HeLa Cell Nuclear Extract
G. Wang (2001)
10.1016/S0891-5849(00)00223-9
Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades.
A. Hubbard (2000)
Mol Diagn
(2001)
10.1186/1471-2105-7-16
Automatic discovery of cross-family sequence features associated with protein function
M. Brameier (2005)
Moon A: p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells
Ms Kim (2003)
10.1007/BF00993106
Selecting a classification method by cross-validation
Cullen Schaffer (2004)
10.1023/A:1022639714137
Technical Note: Selecting a Classification Method by Cross-Validation
Cullen Schaffer (2004)
10.1038/35024111
TFIIH is negatively regulated by cdk8-containing mediator complexes
S. Akoulitchev (2000)
10.1186/1476-4598-3-5
Sensitivity and reproducibility of standardized-competitive RT-PCR for transcript quantification and its comparison with real time RT-PCR
V. Pagliarulo (2003)
10.1073/pnas.132598099
DT40 cells lacking the Ca2+-binding protein annexin 5 are resistant to Ca2+-dependent apoptosis
T. E. Hawkins (2002)
Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand
M Shibuya (2003)
Molecular staging of bladder can
AP Mitra (2005)
10.1016/S0022-5347(06)00181-9
Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.
Y. Lotan (2005)
World Health Organization: The World Health Report 2004 – changing history National Cancer Institute medNews: Treatment Statement for Health Professionals – Bladder Cancer
(2004)
10.1148/RADIOLOGY.143.1.7063747
The meaning and use of the area under a receiver operating characteristic (ROC) curve.
J. Hanley (1982)
10.1074/jbc.M411625200
H-Ras-specific Activation of Rac-MKK3/6-p38 Pathway
I. Shin (2005)
Bladder cancer in Europe
JE Tyczynski (2003)
10.1007/0-387-23254-0_1
Genetic Programming: Theory and Practice
T. Soule (2003)
p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells.
Mi-Sung Kim (2003)
10.1073/PNAS.92.19.8871
Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C.
J. Tassan (1995)
10.1016/J.YEXCR.2004.10.004
The p38 SAPK pathway is required for Ha-ras induced in vitro invasion of NIH3T3 cells.
A. Behren (2005)
Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice.
J. Palumbo (2002)
10.1016/S0090-4295(99)00156-9
Expression of vascular endothelial growth factor receptors in human prostate cancer.
F. Ferrer (1999)
10.1007/978-1-4419-8983-3_3
Classification of Gene Expression Data with Genetic Programming
J. Driscoll (2003)
10.1016/S0006-291X(02)00243-7
Multiplex standardized RT-PCR for expression analysis of many genes in small samples.
E. Crawford (2002)
10.1159/000068773
Potential Value of Soluble Intercellular Adhesion Molecule-1 in the Serum of Patients with Bladder Cancer
G. Ozer (2003)
10.1007/978-1-4419-8983-3_7
What Makes a Problem GP-Hard?
J. M. Daida (2003)
10.1145/967900.968104
Genetic Programming for data classification: partitioning the search space
J. Eggermont (2004)
Activation and signaling of the p38 MAP kinase pathway
TylerZARUBIN (2005)
10.1093/CARCIN/BGI070
Role of ICAM1 in invasion of human breast cancer cells.
C. Rosette (2005)
Role of ICAM 1 in invasion of human breast cancer cells
RB Roth (2005)
10.1038/ng1061
Identifying distinct classes of bladder carcinoma using microarrays
L. Dyrskjøt (2003)
On the uniform convergence of relative frequencies of events to their probabilities. Theory Probab Apl
Vn Vapnik (1971)
10.1198/jasa.2004.s339
The Elements of Statistical Learning: Data Mining, Inference, and Prediction
D. Ruppert (2004)
10.1016/S0020-0255(97)10011-1
A Parallel Implementation of Genetic Programming that Achieves Super-Linear Performance
D. Andre (1996)
10.1016/S0027-5107(01)00194-4
Validation of biomarkers as early predictors of disease.
S. Bonassi (2001)
10.1002/(SICI)1097-0258(19971015)16:19<2143::AID-SIM655>3.0.CO;2-3
Smooth non-parametric receiver operating characteristic (ROC) curves for continuous diagnostic tests.
K. Zou (1997)
10.1046/j.1365-2559.2003.01690.x
Non‐endothelial KDR/flk‐1 expression is associated with increased survival of patients with urothelial bladder carcinomas
H. Gakiopoulou-Givalou (2003)
10.1159/000401187
The urinary bladder.
W. Zontine (1975)
10.1046/j.1464-410x.2000.00614.x
Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis
J. Leissner (2000)
Denis- senko MF: Role of ICAM1 in invasion of human breast cancer cells
C Rosette (2005)
10.1007/11526018_29
Cancer Prediction Using Diversity-Based Ensemble Genetic Programming
J. Hong (2005)
Bladder cancer in Europe. ENCR Cancer Fact Sheets
Je Tyczynski (2003)



This paper is referenced by
Ã˛¸¯˚"¸fl—˝˛-ˆ¯˝¯"¨◊¯—˚¨¯ ˇ—˛ˆ˝˛—"¨◊¯—˚¨¯ ÿ—˚¯—¤ —¿˚¿ Ã˛◊¯´˛ˆ˛ ˇ"˙¤—fl (˛`˙˛— ¸¨"¯—¿""—¤)
A. A. Izmaylov (2011)
10.1053/j.seminoncol.2012.08.008
Prognostic value of cell-cycle regulation biomarkers in bladder cancer.
A. P. Mitra (2012)
10.1007/978-3-319-93339-9_8
Molecular Prognostication in Bladder Cancer.
A. P. Mitra (2018)
Bioinformatics analysis of 'omics' data towards cancer diagnosis and prognosis.
J. Yu (2007)
Expression of VEGF and its receptors VEGFR1/VEGFR2 is associated with invasiveness of bladder cancer.
Pradeep Kumar Kopparapu (2013)
10.1586/14737140.2013.850847
Lymph node-positive bladder cancer: surgical, pathologic, molecular and prognostic aspects
J. Pedrosa (2013)
10.1016/j.ucl.2015.01.003
Potential role for targeted therapy in muscle-invasive bladder cancer: lessons from the cancer genome atlas and beyond.
A. P. Mitra (2015)
10.1586/era.11.60
Molecular signatures that predict nodal metastasis in bladder cancer: does the primary tumor tell tales?
A. P. Mitra (2011)
10.1007/978-3-319-16030-6_1
Application of Machine-Learning Methods to Understand Gene Expression Regulation
Chao Cheng (2014)
10.3233/CBM-171040
Annexin A5 overexpression might suppress proliferation and metastasis of human uterine cervical carcinoma cells.
X. Li (2018)
10.1016/j.neucom.2017.01.126
Computational intelligence approaches for classification of medical data: State-of-the-art, future challenges and research directions
A. Kalantari (2018)
10.1016/j.pharmthera.2017.02.008
Inhibitors of cyclin‐dependent kinases as cancer therapeutics
S. Whittaker (2017)
Estimation of suspended sediment yield flowing into Inanda Dam using genetic programming
A. T. Jaiyeola (2016)
10.1373/CLINCHEM.2006.078154
Quality-controlled measurement methods for quantification of variations in transcript abundance in whole blood samples from healthy volunteers.
E. H. Peters (2007)
10.1002/cncr.27763
Combination of molecular alterations and smoking intensity predicts bladder cancer outcome
A. P. Mitra (2013)
10.1016/j.cca.2013.09.048
Annexin A5 as a potential marker in tumors.
B. Peng (2014)
10.1002/cncr.27628
Generation and external validation of a tumor-derived 5-gene prognostic signature for recurrence of lymph node-negative, invasive colorectal carcinoma
P. Lenehan (2012)
10.1016/j.biopha.2016.09.086
Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin.
Xujuan Sun (2016)
Resolución de problemas de optimización combinatoria utilizando técnicas de computación evolutiva: una aplicación a la biomedicina
Vanessa Aguiar Pulido (2014)
MiRNA-26b inhibits cellular proliferation by targeting CDK8 in breast cancer.
J. Li (2014)
10.7717/peerj.2482
A genetic programming approach to oral cancer prognosis
M. S. Tan (2016)
10.1007/s10555-009-9196-5
Strategies for molecular expression profiling in bladder cancer
A. P. Mitra (2009)
10.1007/978-3-319-16030-6_4
SKGP: The Way of the Combinator
William P. Worzel (2014)
10.1002/path.4596
Cdk8 deletion in the ApcMin murine tumour model represses EZH2 activity and accelerates tumourigenesis
M. McCleland (2015)
10.1016/j.ejca.2013.04.033
A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine.
M. Birkhahn (2013)
10.1016/j.urolonc.2009.08.008
A gene signature of primary tumor identifies metastasized seminoma.
M. Port (2011)
Using Genetic Algorithm to solve Median Problem and Phylogenetic Inference
N. Gao (2014)
10.1016/j.biocel.2008.09.025
Applications of genetic programming in cancer research.
W. Worzel (2009)
10.7554/eLife.20722
Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases
P. Clarke (2016)
10.1002/9781118275436.CH34
Molecular Pathology of Bladder Cancer
L. Cheng (2012)
10.4161/cc.24003
Tumor-suppressive effects of CDK8 in endometrial cancer cells
Weiting Gu (2013)
10.1093/bioinformatics/btn644
A genetic programming-based approach to the classification of multiclass microarray datasets
K. Liu (2009)
See more
Semantic Scholar Logo Some data provided by SemanticScholar