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RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 09 October 2009

Abstract

Purpose

To identify the DNA methylation biomarkers for the detection of the stage I non-small cell lung cancer (NSCLC).

Materials and methods

The methylated state of p16INK4A, ESR1, HOX9, RASSF1A, DAPK1, PTEN, ABCB1, MGMT, APC and MT1G genes that have been reported frequently methylated in lung cancer was determined using methylation-specific PCR in four lung cancer cell lines, 124 cancer tissues of the stage I NSCLC and 26 non-cancerous disease tissues.

Result

The RASSF1A (53/124, 42.74%), APC (49/123, 39.52%), ESR1 (37/124, 29.84%), ABCB1 (31/124, 24.19%, MT1G (25/124, 20.16%) and HOXC9 (17/124, 13.71%) genes were more frequently methylated in the lung tissue from the stage I NSCLC than the non-cancerous lesion patients (2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.05; 1/26, 3.85% P < 0.01; 0/26 0%, P value: <0.01; 0/26, 0%, P < 0.05, respectively). p16INK4A was methylated in 28/124 (22.56%) of cancer tissues and 2/26 (7.69%) of non-cancerous tissues (P value >0.05). No significant association between the methylated state of the genes and the smoking, age or the pathologic types (squamous carcinoma, adenoma and the mixed types) was found. However, p16INK4A methylation was more frequently detected in the male (23/80, 28.75%) than the female (5/44, 11.36%, P > 0.05) patients. MGMT was barely methylated: 1/67, 1.49%), while DAPK1 and PTEN were not at all methylated in the cancer groups.

Conclusions

Methylation analysis in tissue of RASSF1A, APC, ESR1, ABCB1 and HOXC9 genes confirmed 79.8% of the existing diagnosis for the stage I NSCLC at specificity: 73.1%. The insufficiency of predicting disease onset in China, using the previously recommended targets (MGMT, DAPK1 and PTEN) in the United States reflects a potential disease disparity between these two populations. Alternatively, methylated state of this set of genes may be more specific to the late rather than the early stage of NSCLC.

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Abbreviations

APC:

Adenomatous polyposis coli

DAPK1:

Death-associated protein kinase 1

p16INK4A:

Cyclin-dependent kinase inhibitor 2A

PTEN:

Phosphatase and tensin homolog

RASSF1A:

RAS association family 1A

ABCB1:

ATP-binding cassette, subfamily B, member 1

MGMT:

O(6)-methylguanine-DNA-methyltransferase

ESR1:

Estrogen receptor alpha

HOXC9:

Homeobox C9

MT1G:

Metallothionein 1G

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Acknowledgments

This work is supported to J. Zhu by Shanghai Science Foundation grant: 07JC14074, National Science Foundation grants 30570850 and 90919024, 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.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of General Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, 200030, Shanghai, China

    Qiang Lin & Junfeng Geng

  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

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

  3. The First Hospital Affiliated to Suzhou University, 215006, Suzhou, Jiangsu, China

    Zhenya Shen

  4. Division of Basic Research, Shanghai Chest Hospital, Shanghai Jiaotong University, 200030, Shanghai, China

    Guoliang Bao

  5. Department of Urology, Guangxi Medical University, Tumor Hospital, Nanning, 530022, China

    Xu Feng

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

    Jingde Zhu

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  1. Qiang Lin
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  2. Junfeng Geng
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Corresponding author

Correspondence to Jingde Zhu.

Additional information

Q. Lin, J. Geng, K. Ma and J. Yu have contributed equally to this work.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00432-009-0696-z

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Lin, Q., Geng, J., Ma, K. et al. RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. J Cancer Res Clin Oncol 135, 1675–1684 (2009). https://doi.org/10.1007/s00432-009-0614-4

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