Copy number gains at chr3p25 and chr11p11 are associated with lymph node involvement and survival in muscle-invasive bladder tumors

Patients with muscle-invasive bladder cancer (MIBC) have poorer prognoses if cancer has metastasized to the lymph nodes. Genomic markers of lymph node involvement (LNI) would be useful for treatment planning, especially if measured at the biopsy stage, but large-scale studies of tumor tissue at any...

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Bibliographic Details
Published in:PloS one 2017-11, Vol.12 (11), p.e0187975-e0187975
Main Authors: Lindquist, Karla J, Sanford, Thomas, Friedlander, Terence W, Paris, Pamela L, Porten, Sima P
Format: Article
Language:English
Subjects:
Binding sites
Biology and Life Sciences
Biometrics
Biopsy
Bladder
Bladder cancer
Cancer
Copy number
Copy number variations
Data processing
Decisions
Deoxyribonucleic acid
DNA
Gene expression
Genes
Genetic aspects
Genomes
Hematology
Histology
Invasiveness
Lymph nodes
Lymphatic system
Markers
Mathematical models
Medical prognosis
Medicine and Health Sciences
Methyl isobutyl carbinol
Pathology
Patients
Physiological aspects
Ploidy
Prognosis
Regression analysis
Risk factors
Surgery
Survival
Tumors
Urinary bladder
Urology
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Summary:Patients with muscle-invasive bladder cancer (MIBC) have poorer prognoses if cancer has metastasized to the lymph nodes. Genomic markers of lymph node involvement (LNI) would be useful for treatment planning, especially if measured at the biopsy stage, but large-scale studies of tumor tissue at any stage are needed to discover robust markers of LNI. We performed a genome-wide query of copy number alterations (CNA) in 237 MIBC surgical tumor specimens from patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy without neoadjuvant treatment. Pathology reports were independently reviewed to confirm LNI, and copy number data was analyzed to confirm gene-level gains and losses while adjusting for tumor purity and ploidy. Using logistic regression and elastic net models, we identified the CNA most significantly associated with LNI. Multivariable logistic regression was used to describe these CNA associations while adjusting for clinical variables. Kaplan-Meier and Cox regression were used to describe their association with overall survival. Gains in 26 genes were identified as having strong associations with LNI. After adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined, gains in 22 genes on chr3p25 or chr11p11 remained significantly associated with LNI (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0187975