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Analysis of genetic aberrations on chromosomal region 8q21–24 identifies E2F5 as an oncogene with copy number gain in prostate cancer

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Abstract

The copy number gain of genes in chromosomal region 8q21–24 has been demonstrated to be associated with genesis and progression of prostate cancer (PCa). The aim of this study was to identify novel and effective molecular markers in this chromosomal region for PCa. The differentially expressed genes in PCa specimens were screened by gene microarray analysis, which was validated by RT-QPCR analysis. Then, the DNA qPCR analysis was carried out to detect the copy number changes of these differentially expressed genes. Moreover, the clinical significance of candidate markers (MYC and E2F5) in PCa were further determined. E2F5 and MYC were identified as candidate markers in PCa tissues and PCa cell lines. The DNA qPCR revealed the significant copy number gains of E2F5 and MYC in PCa tissues but not in PCa cell lines. In addition, Western blot analysis and immunohistochemical staining both found the significant higher expression of E2F5 and MYC proteins in PCa tissues than those in adjacent benign specimens (all P < 0.01). Moreover, the overexpression of E2F5 protein was significantly associated with a high Gleason score (P < 0.01), an advanced clinical stage (P = 0.01), a positive metastasis (P < 0.01) and PSA Failure (P < 0.01). The overexpression of MYC was more frequently found in PCa tissues with positive metastasis (P = 0.02) and PSA failure (P = 0.02). Interestingly, there was a close correlation in the expression level of MYC in PCa tissues with that of E2F5 (r s  = 0.5, P ≤ 0.001). Our data offers the convincing evidence that the copy number gains of E2F5 and MYC may play an important role in genesis and progression of PCa. Especially, E2F5 may be a novel potential candidate marker for malignant PCa.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81170699), the Guangzhou Municipal Science and Technology Key Project (11C23150711), the Key Projects of Bureau of Health in Guangzhou Municipality (201102A212015), Projects of Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, and the Projects of Guangdong Key Laboratory of Urology (2010A060801016).

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Authors and Affiliations

  1. State Key Lab of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China

    Jin Zhao

  2. Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China

    Jin Zhao, Xin-yang Wu, Xiao-hui Ling & Weide Zhong

  3. Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China

    Xin-yang Wu

  4. Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Department of Urology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Jin Zhao, Zhuo-yuan Lin, Xin Fu, Ye-han Deng, Hui-chan He & Weide Zhong

  5. Urology Key Laboratory of Guangdong Province, Guangzhou Medical University, Guangzhou, 510230, China

    Weide Zhong

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  1. Jin Zhao
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  2. Xin-yang Wu
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Correspondence to Weide Zhong.

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Jin Zhao, Xin-yang Wu and Xiao-hui Ling contributed equally to this article.

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Zhao, J., Wu, Xy., Ling, Xh. et al. Analysis of genetic aberrations on chromosomal region 8q21–24 identifies E2F5 as an oncogene with copy number gain in prostate cancer. Med Oncol 30, 465 (2013). https://doi.org/10.1007/s12032-013-0465-3

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  • DOI: https://doi.org/10.1007/s12032-013-0465-3

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