Gene signatures for the prediction of response to Bacillus Calmette-Guerin immunotherapy in primary pT1 bladder cancers.
OBJECTIVE
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is effective in the prevention of recurrence and progression in many cases of nonmuscle invasive bladder cancer, but many patients fail to respond. The aim of this study was to identify gene sets of markers that could predict the response to BCG immunotherapy in primary pT1 bladder cancer using microarray gene expression profiling.


METHODS
We used 80 patients with primary pT1 bladder cancer treated with BCG immunotherapy as training (48) and test (32) sets. Microarray gene expression profiling was done in the training set to identify genes differentially expressed between responder and nonresponder to BCG immunotherapy according to the events (recurrence or progression). Using a real-time reverse-transcriptase PCR, our findings were validated in the test set.


RESULTS
In the training set, 424 and 287 genes were significantly associated with recurrence- and progression-free survival, respectively. Functional annotation of these genes included cell-mediated immune response, inflammatory response, cellular growth, and proliferation. From these predictive gene signatures, 24 genes (12 in recurrence and 12 in progression) with the highest score of expression ratio were extracted for validation in the test set. In multivariate regression analyses, predictive gene signatures were the only independent predictors of recurrence (hazard ratio, 3.38; P = 0.048) or progression (hazard ratio, 10.49; P = 0.048) in the test set.


CONCLUSIONS
Predictive gene signatures have diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer.
Kim
Yong-June
YJ
Department of Urology, College of Medicine and BK21 Chungbuk Biomedical Science Center, School of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Ha
Yun-Sok
YS
Kim
Seon-Kyu
SK
Yoon
Hyung Yoon
HY
Lym
Min Su
MS
Kim
Min-Ju
MJ
Moon
Sung-Kwon
SK
Choi
Yung Hyun
YH
Kim
Wun-Jae
WJ
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology* / Q000502:physiology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*