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Hypermethylated SFRP1, but none of other nine genes “informative” for western countries, is valuable for bladder cancer detection in mainland China

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Abstract

Purpose

A 11-gene set by methylation-specific PCR in urine sediments for sensitive/specific detection of bladder cancer has been identified previously. In this study, we have evaluated 10 DNA methylation biomarkers that have been reported informative in western countries for bladder cancer diagnosis for a better set.

Materials and methods

The promoter CpG Islands of the following 10 genes: CDH1, FANCF, LOXL1, LOXL4, p16INK4, SFRP1, SOX9, TIG1, TIMP3, and XAF1 have been subjected to methylation-specific PCR analysis in the DNA of 2 bladder cancer cell lines, 2 normal bladder tissues and urine sediments of 82 bladder cancer patients, 15 non-cancerous urogenital patients and 5 healthy volunteers.

Results

Both XAF1 and LOXL1 genes were heterozygously methylated in the normal bladder tissues, showing no cancer state specificity. While the hypermethylated states were detected in urine sediments of bladder cancer at a frequency not less than 2.4% (2/82 cases), nine genes were also methylated in the patients of the non-cancerous urogenital diseases. The methylated SFRP1 was detected in 36.6% (30/82 cases) of bladder cancer and 6.7% (1/15 cases) of non-cancerous urogenital diseases, showing the bladder cancer specificity.

Conclusions

Inclusion of the SFRP1 gene into a set of 11 genes has improved the bladder cancer detection. The insufficiency of predicting disease onset in this study with the previously recommended targets in western countries suggests a possible disease disparity between these two populations. Alternatively, the tissue-specific methylation might be mistaken as the cancer specific in the studies where no non-cancerous lesion controls were involved.

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Acknowledgments

This work is supported to J. Zhu by Shanghai Science Foundation grant: 07DJ14074, National Science Foundation grants 30570850 and 10574134, National Research Program for Basic Research of China grants 2004CB518804, 2009CB825606 and 2009CB825607, European 6th program grant LSHB-CT-2005-019067 and supported to J. Yu by National Science Foundation grant: 30872963. Thanks are due to Q. Li for the statistic analysis.

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Authors and Affiliations

  1. School of Medicine, Fudan University, 200032, Shanghai, China

    Jinfeng Sun & Kelong Ma

  2. Cancer Epigenetics and Gene Therapy Program, The State-Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiaotong University, LN 2200/25, Xietu Road, 200032, Shanghai, China

    Jinfeng Sun, Jian Yu, Kelong Ma, Hongyu Zhang, Yinghua He, Xiaoying Luo & Jingde Zhu

  3. Department of Urology, Zhongshan Hospital Affiliated to Fudan University, 200032, Shanghai, China

    Zhou Chen & Tongyu Zhu

  4. Cancer Epigenetics Laboratory, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, China

    Jingde Zhu

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  1. Jinfeng Sun
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Correspondence to Jingde Zhu.

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J. Sun, Z. Chen, T. Zhu and J. Yu contributed equally to this work.

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Sun, J., Chen, Z., Zhu, T. et al. Hypermethylated SFRP1, but none of other nine genes “informative” for western countries, is valuable for bladder cancer detection in mainland China. J Cancer Res Clin Oncol 135, 1717–1727 (2009). https://doi.org/10.1007/s00432-009-0619-z

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  • DOI: https://doi.org/10.1007/s00432-009-0619-z

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