Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer.
BACKGROUND
While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer.


RESULTS
We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression.


CONCLUSIONS
We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.
Kim
Wun-Jae
WJ
Department of Urology, College of Medicine, Chungbuk National University, Chungbuk, South Korea. wjkim@chungbuk.ac.kr
Kim
Eun-Jung
EJ
Kim
Seon-Kyu
SK
Kim
Yong-June
YJ
Ha
Yun-Sok
YS
Jeong
Pildu
P
Kim
Min-Ju
MJ
Yun
Seok-Joong
SJ
Lee
Keon Myung
KM
Moon
Sung-Kwon
SK
Lee
Sang-Cheol
SC
Cha
Eun-Jong
EJ
Bae
Suk-Chul
SC
D000368:Aged; D016000:Cluster Analysis; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*