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Circulating Methylated MINT2 Promoter DNA Is a Potential Poor Prognostic Factor in Gastric Cancer

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Abstract

Background and Aim

Aberrant DNA methylation has been shown to be associated with the growth, development, metastasis, and prognosis of tumors. Methylated DNAs may be suitable biomarkers for cancer patients. Here, we investigated whether circulating methylated MINT2 DNAs represent a potential poor prognostic factor in gastric cancer (GC).

Methods

MINT2 methylation was detected by real-time methylation-specific PCR in tumor tissues, pairing preoperative peritoneal lavage fluid (PPLF) and blood from 92 GC patients. The theory meaning and clinical practicality value of MINT2 methylation in different specimens were analyzed.

Results

The methylation status of the MINT2 gene was found to be significantly higher in tumor tissues (44.6 %, 41/92) than in adjacent normal tissues (3.3 %, 3/92). No MINT2 methylation was found in healthy controls, and partial MINT2 methylation was observed in three (6.25 %, 3/48) patients with chronic atrophic gastritis. The frequency of MINT2 methylation in pairing PPLF and blood samples from 92 GC patients was 40.2 % (37/92) and 39.1 % (36/92), respectively. Methylated MINT2 in tumor tissues, pairing PPLF, and blood samples were very approximate. Aberrant MINT2 methylation in tumor tissues and pairing PPLF or blood samples were closely related to peritoneal dissemination, tumor progression, and poor prognosis (all P < 0.0001).

Conclusions

Aberrant MINT2 methylation in PPLF/blood may predict peritoneal micrometastasis for GC patients, which is a potential poor prognostic factor in GC.

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Acknowledgments

This research was supported by a grant from the program for New Century Excellent Talents in University, from the Ministry of Education, China (NCET-11-0949), a grant from the Science and Technology General Project of Zhejiang Province (No. 2009C33143), Key Research Projects of Medicine, from the Ministry of Health, China (No. WKJ2010-2-004), partly by a grant from the Backbone Talent of Zhejiang Provincial Medicine and Hygiene Platform Programs (No. 2011RCA009), a grant from the Scientific and Technological Innovations Fund of Henan Province Higher Education (No. 2009HAST1T001), and by a grant from the Science and Technology Key Project of the Ministry of Education, China (No. 210130).

Conflict of interest

None.

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Authors and Affiliations

  1. Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No. 38 Guangji Rd., Banshanqiao District, Hangzhou, 310022, People’s Republic of China

    Jing Han, Ping Lv, Jiang-Liu Yu, Yi-Chen Wu, Xin Zhu, Lian-Lian Hong, Wang-Yu Zhu & Zhi-Qiang Ling

  2. The Central Laboratory, Zhoushan Hospital, Zhoushan, 316000, People’s Republic of China

    Wang-Yu Zhu

  3. Department of Surgical Oncology, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No. 38 Guangji Rd., Banshanqiao District, Hangzhou, 310022, People’s Republic of China

    Qi-Ming Yu & Xin-Bao Wang

  4. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China

    Pei Li

  5. Department of Surgical Oncology, Zhoushan Hospital, Zhoushan, 316000, People’s Republic of China

    Ping Lv

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  1. Jing Han
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  2. Ping Lv
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  3. Jiang-Liu Yu
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  11. Zhi-Qiang Ling
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Corresponding author

Correspondence to Zhi-Qiang Ling.

Additional information

Jing Han and Ping Lv wish it to be known that, in their opinion, the first two authors should be regarded as joint-first authors.

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Han, J., Lv, P., Yu, JL. et al. Circulating Methylated MINT2 Promoter DNA Is a Potential Poor Prognostic Factor in Gastric Cancer. Dig Dis Sci 59, 1160–1168 (2014). https://doi.org/10.1007/s10620-013-3007-0

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  • DOI: https://doi.org/10.1007/s10620-013-3007-0

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