Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors.
OBJECTIVE
In approximately 20% of patients with superficial bladder tumors, the tumors progress to invasive tumors after treatment. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. We aim to identify a molecular signature that can reliably identify patients with high-risk superficial tumors that are likely to progress to invasive tumors.


METHODS
Gene expression data were collected from tumor specimens from 165 patients with bladder cancer. Various statistical methods, including leave-one-out cross-validation methods, were applied to identify a gene expression signature that could predict the likelihood of progression to invasive tumors and to test the robustness of the expression signature in an independent cohort. The robustness of the gene expression signature was validated in an independent (n = 353) cohort.


RESULTS
Supervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. A molecular classifier based on this gene expression signature correctly predicted the likelihood of progression of superficial tumor to invasive tumor.


CONCLUSIONS
We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.
Lee
Ju-Seog
JS
The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Leem
Sun-Hee
SH
Lee
Sang-Yeop
SY
Kim
Sang-Cheol
SC
Park
Eun-Sung
ES
Kim
Sang-Bae
SB
Kim
Seon-Kyu
SK
Kim
Yong-June
YJ
Kim
Wun-Jae
WJ
Chu
In-Sun
IS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D003558:Cystoscopy / Q000379:methods; D018450:Disease Progression; D050703:E2F2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012334:RNA, Neoplasm / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D055815:Young Adult
D050703:E2F2 Transcription Factor; D012334:RNA, Neoplasm