PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer

Donkena Krishna Vanaja, Karla V. Ballman, Bruce W. Morlan, John C. Cheville, Roxann M. Neumann, Michael M. Lieber, Donald J. Tindall, Charles Y.F. Young

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Abstract

Purpose: We analyzed the expression of genes to identify reliable molecular markers in the diagnosis and progression of prostate cancer. Experimental Design: Gene expression profiling was done using HG-U133 set microarrays in 32 prostate cancer and 8 benign tissues of patients with cancer. Expression levels of 11 genes were selected for quantitative real-time PCR evaluation in 52 prostate cancer and 20 benign tissues. Further, to assess transcriptional inactivation, we analyzed the promoter methylation of genes by quantitative methylation-specific PCR in 62 tumor and 36 benign tissues. Results: Our results showed a significant down-regulation in the mRNA expression levels of PRIMA1, TU3A, PDLIM4, FLJ14084, SVIL, SORBS1, C21orf63, and KIAA1210 and up-regulation of FABP5, SOX4, and MLP in prostate cancer tissues by TaqMan real-time PCR. Quantitative methylation-specific PCR of PDLIM4, SVIL, PRIMA1, GSTP1, and PTGS2 detected prostate carcinoma with a sensitivity of 94.7%, 75.4%, 47.4%, 89.5%, and 87.7%, and a specificity of 90.5%, 75%, 54.2%, 95.8%, and 90.2%, respectively. Using this panel of methylation markers in combination, we were able to distinguish between prostate cancer and adjacent benign tissues with sensitivities and specificities of about 90% to 100%. Our data provide evidence of transcriptional repression of the putative tumor suppressor gene PDLIM4 by hypermethylation. Conclusions: Our analysis revealed differential expression of eight down-regulated and three up-regulated genes, implicating their role in prostate cancer development and progression. We further showed that the hypermethylation of PDLIM4 gene could be used as a sensitive molecular tool in detection of prostate tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1128-1136
Number of pages9
JournalClinical Cancer Research
Volume12
Issue number4
DOIs
StatePublished - Feb 15 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vanaja, D. K., Ballman, K. V., Morlan, B. W., Cheville, J. C., Neumann, R. M., Lieber, M. M., Tindall, D. J., & Young, C. Y. F. (2006). PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. Clinical Cancer Research, 12(4), 1128-1136. https://doi.org/10.1158/1078-0432.CCR-05-2072