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Hypermethylation of IFN-γ in oral cancer tissues

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Abstract

Objectives

The study aimed to evaluate the methylation pattern of the interferon-gamma (IFN-γ) gene in oral cancer tissues compared with normal and benign oral disease tissues.

Materials and methods

The oral tissues were gained from the patients of 85 cases of oral squamous cell carcinoma (OSCC), 47 cases of oral dysplastic lesions, and 53 normal biopsies. IFN -γ methylation in oral tissues was verified through methylation-specific polymerase chain reaction (PCR) and DNA sequencing analyses, and the expression levels of IFN-γ messenger RNA (mRNA) and protein were detected using real-time reverse transcription (RT)-PCR and enzyme-linked immunosorbent assays, respectively. IFN-γ was localized in macrophages from oral tissues and detected via immunostaining.

Results

IFN-γ mRNA and protein expression levels were evidently decreased in oral cancer tissues, whereas the IFN-γ methylation rate was significantly higher in malignant tumors than in benign and normal tissues (normal, 22.6%; benign, 38.3%; and cancer, 55.3%; P < 0.05). Furthermore, the expression of IFN-γ mRNA was significantly downregulated in oral tumors with methylation compared with tumors without methylation, as determined by real-time RT-PCR (4.76-fold difference; P < 0.05). Likewise, mRNA expression was downregulated by 6.79-fold in oral epithelial dysplasia tissues with methylation compared with those without methylation (P < 0.01). Co-immunostaining to detect MAC2 and IFN-γ demonstrated that macrophages comprised the main source of IFN-γ in oral tissues. IFN-γ methylation demonstrated a significant association with the clinical stage, histopathology grade, and primary tumor.

Conclusions

Aberrant IFN-γ promoter methylation may be involved in the process of tumorigenesis of oral cancer.

Clinical relevance

IFN-γ hypermethylation during the process of oral carcinogenesis could be useful for the clinical diagnosis and treatment for OSCC.

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Authors and Affiliations

  1. Department of Oral Medicine, The Second Hospital of Hebei Medical University, Heping Western Road 215, Shijiazhuang, Hebei, 050000, People’s Republic of China

    Songbo Tian

  2. Department of Thoracic Surgery, Tianjin Union Medical Center, 190 Jieyuan Road, Hongqiao District, Tianjin, Tianjin, 300121, People’s Republic of China

    Chunyang Jiang

  3. Department of Nephrology, Hongqi Hospital, Mudanjiang Medical College, 5 Tongxiang Road, Aimin District, Mudanjiang, Heilongjiang, 157011, People’s Republic of China

    Xiaoqin Liu

  4. Department of Neurosurgery, Tangshan People’s Hospital, Tangshan, Hebei, 063001, People’s Republic of China

    Sheng Xu

  5. Department of Physical Examination, The Second Hospital of Hebei Medical University, Heping Western Road 215, Shijiazhuang, Hebei, 050000, People’s Republic of China

    Zhiyong Zhang, Huizhen Chen, Yinghuai Zhang & Yanping Liu

  6. School of Public Health, North China University of Science and Technology, Jianshe Road 57, Tangshan, Hebei, 063000, People’s Republic of China

    Dong Ma

Authors
  1. Songbo Tian
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  2. Chunyang Jiang
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  3. Xiaoqin Liu
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  4. Sheng Xu
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  5. Zhiyong Zhang
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  6. Huizhen Chen
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  7. Yinghuai Zhang
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  8. Yanping Liu
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  9. Dong Ma
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Corresponding authors

Correspondence to Chunyang Jiang, Yanping Liu or Dong Ma.

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Conflict of interest

The authors declare that they have no competing interests.

Funding

This work was supported by grants from the National Nature Science Foundation of China (No. 81541149) and the Tianjin health and Tianjin Health and Family Planning Commission of Science and Technology Project Foundation (No. 16KG153).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee of the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Songbo Tian, B.D., Chunyang Jiang, Xiaoqin Liu, and Sheng Xu contributed equally to this work.

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Cite this article

Tian, S., Jiang, C., Liu, X. et al. Hypermethylation of IFN-γ in oral cancer tissues. Clin Oral Invest 21, 2535–2542 (2017). https://doi.org/10.1007/s00784-017-2052-z

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  • DOI: https://doi.org/10.1007/s00784-017-2052-z

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