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

Abstract

Objectives

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.

Results

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.

Conclusion

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.

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Abbreviations

BMSCC :

Buccal mucosal squamous cell carcinoma

CTAN :

Corresponding tumor adjacent normal

DFS :

Disease-free survival

DSS :

Disease-specific survival

IFN :

Interferon

IHC :

Immunohistochemistry

LCM :

Laser capture microdissection

LSCC :

Lip squamous cell carcinoma

OSCC:

Oral squamous cell carcinoma

TSCC :

Tongue squamous cell carcinoma

NGS :

Next-generation sequencing

TMA :

Tissue microarray

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Funding

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).

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Correspondence to Pei-Feng Liu.

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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.

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Liu, PF., Chen, HC., Shu, CW. et al. Guanylate-binding protein 6 is a novel biomarker for tumorigenesis and prognosis in tongue squamous cell carcinoma . Clin Oral Invest 24, 2673–2682 (2020). https://doi.org/10.1007/s00784-019-03129-y

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Keywords

  • Oral squamous cell carcinoma
  • Guanylate-binding protein 6
  • Tumorigenesis
  • Prognosis