Abstract
Simple SummaryThe survival rate of oral squamous cell carcinoma (OSCC) patients has not been improved in the past few decades, likely as a result of a lack of therapeutic targets. Through next generation sequencing for tumor tissues of OSCC patients, the gene expression level of guanylate binding protein 5(GBP5) was significantly elevated in tumor tissues compared with adjacent normal tissues and associated with poor prognosis in OSCC patients. Moreover, we found that GBP5 modulated cell cycle, invasion/migration, and cancer stemness in OSCC cells. Our study indicated that GBP5 might be a potential biomarker and therapeutic target for OSCC patients.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.
Highlights
Oral squamous cell carcinoma (OSCC) accounts for 90% of all head and neck squamous cell carcinoma (HNSCC) [1] and covers three major histological regions, including buccal mucosal squamous cell carcinoma (BMSCC), tongue squamous cell carcinoma (TSCC), and lip squamous cell carcinoma (LSCC)
After filtering genes by RPKM and fold change, we found that gene expression levels of Guanylate binding protein 5 (GBP5) were increased by 9.10-fold and 6.59-fold in stages I (T1) and stages IV (T2) tumor tissues, respectively, compared with those in corresponding tumor adjacent normal tissues (CTAN) tissues (N1 and N2) (Figure 1A)
We found that high gene expression levels of GBP5 were associated with shorter overall survival (OS) in oral cancer patients with poor cell differentiation (adjusted hazard ratio (AHR) = 1.49, 95% confidence interval (CI) = 1.01–2.21, p = 0.047, Table 2)
Summary
Oral squamous cell carcinoma (OSCC) accounts for 90% of all head and neck squamous cell carcinoma (HNSCC) [1] and covers three major histological regions, including buccal mucosal squamous cell carcinoma (BMSCC), tongue squamous cell carcinoma (TSCC), and lip squamous cell carcinoma (LSCC). A variety of targeted therapeutic drugs have been tested in OSCC patients [2], the survival rate is still around 50% [3], and nearly up to 40% of OSCC patients subsequently develop recurrences or distant metastases [4]. Identification of more effective and available biomarkers and therapeutic targets for OSCC patients is an unmet need. Aside from the role GBPs play in pathogen defense, an increasing number of studies have focused on investigating the role of GBPs in cancer development and progression. Increased levels of GBP5 expression were found in tumor tissues compared with those in normal tissues, as a higher GBP5 mRNA level is not associated with overall survival and relapse free survival in HNSCC [6]. The role of GBP5 in OSCC is still unclear
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