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Identification of novel serological tumor markers for human prostate cancer using integrative transcriptome and proteome analysis

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Abstract

The aim of this study was to identify novel serological tumor markers for human prostate cancer (PCa). We compared the gene expression profile of PCa tissues to adjacent benign tissues of prostate using gene expression microarray. 1207 genes that were consistently different from adjacent benign tissues of prostate (paired t test, P < 0.05) were selected as differentially expressed genes (DEGs). Among them, 652 DEGs were upregulated in PCa, whereas 555 DEGs were downregulated in PCa. In addition, two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MS was performed to screen for candidate markers in the proteome of PCa and adjacent benign tissues of prostate. A total of 89 spots were significantly up-regulated (ratio ≥ 2, P < 0.01) in PCa samples, whereas 66 spots were down-regulated (ratio ≤ −2, P < 0.01). Sixty gene products were identified among these spots. Moreover, 14 potential candidate markers, which were identified as differentially expressed molecules by both gene expression microarray and 2D-DIGE, were chosen for validation and analysis by ELISA. The serum levels of three proteins correlated well with the 2D-DIGE results. Furthermore, the increased serum level of Inosine monophosphate dehydrogenase II (IMPDH2) was significantly associated with the clinicopathological features of the patients with PCa, suggesting its potential as a serological tumor marker. These results demonstrated that integrative transcriptome and proteome analysis could be a powerful tool for marker discovery in PCa. We suggest IMPDH2 as a novel serological tumor marker for detection of early PCa and evaluation of tumor progression.

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Acknowledgments

This work was funded by National Natural Science Foundation of China (30872960, 81170699), Chinese National Key Program of Basic Research (2010CB912700, 2011CB910601), National S&T Major Project (2008ZX10002-016, 2009ZX09301-002), Guangzhou Municipal Science and Technology Key Project (11C23150711), Key Projects of Bureau of Health in Guangzhou Municipality (201102A212015) and Projects of Guangdong Key Laboratory of Urology (2010A060801016).

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Authors and Affiliations

  1. Department of Urology, Guangzhou First Municipal People’s Hospital, Affiliated Guangzhou Medical College, Guangzhou, 510180, China

    Zhao-dong Han, Hui-chan He, Qi-shan Dai, Guo-qiang Qin, Jia-hong Chen, Chao Cai, Xin Fu & Wei-de Zhong

  2. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Engineering Research Center for Protein Drugs, Beijing, 102206, China

    Yan-qiong Zhang & Yun-ping Zhu

  3. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China

    Yan-qiong Zhang

  4. Department of Urology, Guangdong Provincial People’s Hospital, Guangzhou, 510000, China

    Xue-cheng Bi

  5. Department of Urology, Guizhou Provincial People’s Hospital, Guizhou, 550002, China

    Jian-guo Zhu

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

    Dong-jiang Liao, Xin-peng Lu & Zi-yao Mo

  7. Urology Key Laboratory of Guangdong Province, Guangzhou Medical College, Guangzhou, 510230, China

    Wei-de Zhong

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

    Zhao-dong Han & Wei-de Zhong

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  1. Zhao-dong Han
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  2. Yan-qiong Zhang
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  8. Xin Fu
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Corresponding authors

Correspondence to Yun-ping Zhu or Wei-de Zhong.

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Zhao-dong Han and Yan-qiong Zhang authors contributed equally to this work.

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Han, Zd., Zhang, Yq., He, Hc. et al. Identification of novel serological tumor markers for human prostate cancer using integrative transcriptome and proteome analysis. Med Oncol 29, 2877–2888 (2012). https://doi.org/10.1007/s12032-011-0149-9

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  • DOI: https://doi.org/10.1007/s12032-011-0149-9

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