Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Abstract

Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial−mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.

A novel DNA methylation‐driver gene signature for long‐term survival prediction of hepatitis‐positive hepatocellular carcinoma patients

“…Except for these genes, CASP8, GBP5 and LUCAT1 have been reported to play multiple roles in numerous cancer types, such as head and neck cancer, oral squamous cell carcinoma, esophageal squamous cell carcinoma, colorectal cancer and HCC. 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 For example, recent studies suggested that CASP8 is involved in autophagy‐related apoptosis and can be used as a prognostic marker of HCC together with other molecules, 52 , 53 and GBP5 can be used as a prognostic biomarker of HCC together with other genes, and it is closely related to immune characteristics. 54 Furthermore, LUCAT1 was reported to affecting the proliferation, migration and invasion processes of HCC.…”

Guanylate binding protein 5 is an immune‐related biomarker of oral squamous cell carcinoma: A retrospective prognostic study with bioinformatic analysis

“…The expression of GBP5 was scored semi‐quantitatively based on the staining intensity and extent of cancer and stromal cells, as previously reported. 27 , 28 The staining intensity scores were categorized as negative (0), mild (1), moderate (2), strong (3), while the staining extent as <5% (0), 5 to <25% (1), 25 to <50% (2), 50% to <75% (3), ≥ 75% (4). The total intensity and extent of staining scores in tumor and stromal cells were defined as the GBP5 tumor and GBP5 stromal scores (ranging from 0 to 7), respectively.…”

TMEM211 Promotes Tumor Progression and Metastasis in Colon Cancer

“…The nucleotide sequences of TMEM211 primer (Forward: 5′-GCCTCCTCCATGTATTATGGTG-3′; Reverse: 5′-CCTTGGACCTTGGTTGTGTG-3′) were used in this study. More detailed procedures were described in a previous study [ 39 ].…”