Guanylate-binding protein 6 is a novel biomarker for tumorigenesis and prognosis in tongue squamous cell carcinoma

  • Pei-Feng LiuEmail author
  • Hung-Chih Chen
  • Chih-Wen Shu
  • Huei-Cin Sie
  • Cheng-Hsin Lee
  • Huei-Han Liou
  • Jiin-Tsuey Cheng
  • Kuo-Wang Tsai
  • Luo-Ping Ger
Original Article



Guanylate-binding protein 6 (GBP6) is a member of the guanylate-binding protein family, and its role in cancer has not yet been reported. We aimed to investigate the clinical significance of GBP6 in oral squamous cell carcinoma (OSCC).

Materials and methods

Next-generation sequencing was applied for analyzing differential gene expression profiling between corresponding tumor adjacent normal (CTAN) and tumor tissue from two paired OSCC patients. Real-time PCRs (RT-PCRs) were used to investigate the gene expression level of GBP6 of CTAN and tumor tissue samples from 14 TSCC patients. Immunohistochemistry was used to investigate the protein expression level of GBP6 in tumor tissues and paired CTAN tissues from 488 OSCC patients, including 183 buccal mucosa squamous cell carcinoma (BMSCC), 245 tongue squamous cell carcinoma (TSCC), and 60 lip squamous cell carcinoma (LSCC) patients.


Compared with CTAN tissues of OSCC patients, GBP6 is identified as a downregulated gene using the NGS platform, which was confirmed in 14 OSCC patients by RT-PCR. Moreover, protein expression level of GBP6 in tumor tissues was lower than that in CTAN tissues and the low GBP6 expression was correlated with poor cell differentiation/lymph node metastasis in TSCC patients. In addition, TSCC patients with low expression levels of GBP6 had poor disease-specific survival rate.


The low expression of GBP6 was associated with tumorigenesis and poor prognosis in OSCC patients, especially in TSCC patients.

Clinical relevance

GBP6 may serve as a novel favorable diagnostic and prognostic biomarker in TSCC patients.


Oral squamous cell carcinoma Guanylate-binding protein 6 Tumorigenesis Prognosis 



Buccal mucosal squamous cell carcinoma


Corresponding tumor adjacent normal


Disease-free survival


Disease-specific survival






Laser capture microdissection


Lip squamous cell carcinoma


Oral squamous cell carcinoma


Tongue squamous cell carcinoma


Next-generation sequencing


Tissue microarray


Funding information

This work was supported by grants from the Kaohsiung Veterans General Hospital (VGHKS107-174 and VGHKS108-178), the Ministry of Science and Technology (MOST 106-2320-B-075B-002-MY2 and MOST 108-2320-B-075B-003) and the Yen Tjing Ling Medical Foundation (CI-107-13).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board (IRB) at the Kaohsiung Veterans General Hospital (KVGH, IRB number: VGHKS11-CT12-13) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

Supplementary material

784_2019_3129_MOESM1_ESM.docx (459 kb)
ESM 1 (DOCX 458 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biomedical Science and Environmental BiologyKaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Institute of Biomedical SciencesNational Sun Yat-sen UniversityKaohsiungTaiwan
  3. 3.Department of StomatologyKaohsiung Veterans General HospitalKaohsiungTaiwan
  4. 4.Department of Dental TechnologyShu-Zen Junior College of Medicine and ManagementKaohsiungTaiwan
  5. 5.School of Medicine for International StudentsI-Shou UniversityKaohsiungTaiwan
  6. 6.Department of Pathology and Laboratory MedicineKaohsiung Veterans General HospitalKaohsiungTaiwan
  7. 7.Department of Medical Education and ResearchKaohsiung Veterans General HospitalKaohsiungTaiwan
  8. 8.Department of Biological SciencesNational Sun Yat-Sen UniversityKaohsiungTaiwan

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