TY - JOUR
T1 - Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
AU - Dyrskjot, L
AU - Reinert, T
AU - Novoradovsky, A
AU - Zuiverloon, Tahlita
AU - Beukers, Willemien
AU - Zwarthoff, Ellen
AU - Malats, N
AU - Real, FX
AU - Segersten, U
AU - Malmstrom, PU
AU - Knowles, M
AU - Hurst, C
AU - Sorge, J
AU - Borre, M
AU - Orntoft, TF
PY - 2012
Y1 - 2012
N2 - BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off v CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer. British Journal of Cancer (2012) 107, 1392-1398. doi:10.1038/bjc.2012.412 www.bjcancer.com Published online 13 September 2012 (C) 2012 Cancer Research UK
AB - BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off v CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer. British Journal of Cancer (2012) 107, 1392-1398. doi:10.1038/bjc.2012.412 www.bjcancer.com Published online 13 September 2012 (C) 2012 Cancer Research UK
U2 - 10.1038/bjc.2012.412
DO - 10.1038/bjc.2012.412
M3 - Article
C2 - 22976798
SN - 0007-0920
VL - 107
SP - 1392
EP - 1398
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -