Molecular Medicine

, Volume 17, Issue 5–6, pp 478–485 | Cite as

A Four-Gene Signature Predicts Disease Progression in Muscle Invasive Bladder Cancer

  • Wun-Jae Kim
  • Seon-Kyu Kim
  • Pildu Jeong
  • Seok-Joong Yun
  • In-Chang Cho
  • Isaac Yi Kim
  • Sung-Kwon Moon
  • Hong-Duck Um
  • Yung Hyun Choi
Research Article


There are no reliable criteria to handle disease progression of muscle invasive bladder cancer (MIBC), which strongly influences patient survival. Therefore, an accurate predicting method to identify progressive MIBC patients is greatly needed. The aim of this study was to identify a genetic signature associated with disease progression in MIBC. To address this issue, we analyzed three independent cohorts (a training set, test set 1 and test set 2) comprising a total of 128 MIBC patients. Microarray gene expression profiling, including gene network analysis, was performed in the training set to identify a gene expression signature associated with disease progression. The prognostic value of the signature was validated in test set 1 and test set 2 by microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The determination of gene expression patterns by microarray data analysis identified 1,320 genes associated with disease progression. Gene network analysis of the 1,320 genes suggested that IL1B, S100A8, S100A9 and EGFR were important mediators of MIBC progression. We validated this putative four-gene signature in two independent cohorts (log-rank test, P < 0.05 each, respectively) and estimated the predictive value of the signature by multivariate Cox regression analysis (hazard ratio (HR), 6.24; 95% confidence interval (CI), 1.58-24.61; P= 0.009). Finally, signature-based stratification demonstrated that the four-gene signature was an independent predictor of MIBC progression. In conclusion, a molecular signature defined by four genes represents a promising diagnostic tool for the identification of MIBC patients at high risk of progression.



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0001729).

Supplementary material

10020_2011_1705478_MOESM1_ESM.pdf (1.4 mb)
A Four-Gene Signature Predicts Disease Progression in Muscle Invasive Bladder Cancer


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Wun-Jae Kim
    • 1
    • 2
  • Seon-Kyu Kim
    • 1
    • 2
  • Pildu Jeong
    • 1
    • 2
  • Seok-Joong Yun
    • 1
    • 2
  • In-Chang Cho
    • 3
  • Isaac Yi Kim
    • 4
  • Sung-Kwon Moon
    • 5
  • Hong-Duck Um
    • 6
  • Yung Hyun Choi
    • 7
    • 8
  1. 1.Department of UrologyChungbuk National University College of MedicineHeungduk-ku, Cheongju, ChungbukSouth Korea
  2. 2.BK21 Chungbuk Biomedical Science Center, School of MedicineChungbuk National UniversityCheongju, ChungbukSouth Korea
  3. 3.Center for Prostate CancerNational Cancer CenterGoyang-siSouth Korea
  4. 4.Section of Urologic OncologyCancer Institute of New Jersey, Robert Wood Johnson Medical SchoolNew BrunswickUSA
  5. 5.Department of Food and BiotechnologyChungju National UniversityChungju, ChungbukSouth Korea
  6. 6.Laboratories of Radiation Tumor PhysiologyKorea Institute of Radiological and Medical SciencesSeoulSouth Korea
  7. 7.Department of BiochemistryDongeui University College of Oriental MedicineBusanSouth Korea
  8. 8.Department of Biomaterial Control (BK21 Program)Dongeui University Graduate SchoolBusanSouth Korea

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