Abstract
Aims: Oral squamous cell carcinoma (OSCC) is a common oral cancer; however, current therapeutic approaches still show limited efficacy. Our research aims to explore effective biomarkers related to OSCC.Main methods: Gene expression profiles of paired OSCC tumor and paracancerous samples from The Cancer Genome Atlas (TCGA) were analyzed. mRNA and protein levels of KRT84 in OSCC cell line HSC-3 were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. KRT84 protein levels in OSCC tumor samples of different stages were determined by immunohistochemistry. Overall survival (OS) of OSCC samples was evaluated and association of multiple factors with OS was assessed.Key findings: Compared with paracancerous samples, 4642 DEGs were identified in OSCC tumor samples. Among them, KRT84 expression level in OSCC tumor tissues was obviously decreased, which was validated in HSC-3 cells. KRT84 expression level showed decreasing tendency with the increase of tumor grade and stage. Patients with low KRT84 expression level had inferior OS independently of multiple factors. Besides, antigen processing and presentation pathway were significantly activated in OSCC samples with high KRT84 expression. Elevated KRT84 mRNA as well as protein levels were confirmed by RT-qPCR and Western blot in OSCC and normal cell lines, and immunohistochemistry in OSCC tumor and paracancerous tissues.Significance: Our study suggests KRT84 as a tumor suppressor and good prognostic indicator for OSCC, which might be significant for OSCC diagnosis and treatment.
Highlights
Oral squamous cell carcinoma (OSCC) is recognized as the most common phenotype of oral cancer, accounting for approximately 3% of the malignancies worldwide [1]
After analyzing the gene expression profiles of OSCC samples, a total of 4642 differentially expressed genes (DEGs) were identified between in OSCC tumor samples compared with paracancerous samples, among which 2254 were down-regulated and 2388 were up-regulated in OSCC tumor samples (Figure 1A)
The results showed that the expression level of KRT84 in OSCC tumor samples was significantly lower than that in paracancerous samples
Summary
Oral squamous cell carcinoma (OSCC) is recognized as the most common phenotype of oral cancer, accounting for approximately 3% of the malignancies worldwide [1]. Consumptions of tobacco and alcohol are responsible for almost 90% of the OSCC cases, while oral hygiene, human papillomavirus, and dental status are considered as the risk factors [5]. Despite of the substantial advances in therapeutic approaches of OSCC and improvement in survival status, the overall 5-year survival is only 50–60%, which remains unchanged in recent years. The relatively low overall 5-year survival is partially caused by the limited efficacy of current therapeutic approaches in OSCC, especially for the metastatic OSCC, which is believed to be one of the major risk factors for OSCC mortality [6–8]. Considering the low survival rate and unoptimistic status of OSCC treatment, it is imperative to explore more effective biomarkers for further understanding of OSCC pathogenesis and facilitation of its therapeutic strategies
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