Clinical Oral Investigations

, Volume 21, Issue 8, pp 2535–2542 | Cite as

Hypermethylation of IFN-γ in oral cancer tissues

  • Songbo Tian
  • Chunyang JiangEmail author
  • Xiaoqin Liu
  • Sheng Xu
  • Zhiyong Zhang
  • Huizhen Chen
  • Yinghuai Zhang
  • Yanping LiuEmail author
  • Dong MaEmail author
Original Article



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 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.


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.


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.


Oral cancer Methylation Cytokines IFN-γ Tumorigenesis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Oral MedicineThe Second Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Department of Thoracic SurgeryTianjin Union Medical CenterTianjinPeople’s Republic of China
  3. 3.Department of Nephrology, Hongqi HospitalMudanjiang Medical CollegeMudanjiangPeople’s Republic of China
  4. 4.Department of NeurosurgeryTangshan People’s HospitalTangshanPeople’s Republic of China
  5. 5.Department of Physical ExaminationThe Second Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  6. 6.School of Public HealthNorth China University of Science and TechnologyTangshanPeople’s Republic of China

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