Abstract
Most patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly associated with carcinogenesis and treatment outcomes in oral squamous cell cancer, affecting cell growth and proliferation. Therefore, focusing on DNA repair and genetic instability interactions could be a potential target for improving the outcomes of OSCC patients. DNA polymerase-β (POLB) is an important enzyme in base excision repair and contributes to gene instability, leading to tumorigenesis and cancer metastasis. The aim of our study was to confirm POLB regulates the growth of OSCC cells through modulation of cell cycle and chromosomal instability. We analyzed a tissue array from 133 OSCC patients and discovered that low POLB expression was associated with advanced tumor stage and poor overall survival. In multivariate Cox proportional hazards regression analysis, low POLB expression and advanced lymph node status were significantly associated with poor survival. By performing in vitro studies on model cell lines, we demonstrated that POLB silencing regulated cell cycles, exacerbated mitotic abnormalities and enhanced cell proliferation. After POLB depletion, OSCC cells showed chromosomal instability and aneuploidy. Thus, POLB is an important maintainer of karyotypic stability in OSCC cells.
Highlights
Worldwide, head and neck cancer (HNC) is the sixth commonest cancer, with 90% of the histological type constituted by squamous cell carcinoma [1]
POLB and we used immunohistochemical staining to explore the relationships between andcavity clinicopathological parameters in biopsy specimens from 133 patients with oral clinicopathological parameters in biopsy specimens from patients with oral cavity cancer
We found that the POLB expression in cancer cells from oral squamous cell cancer (OSCC) patients was lower than that in normal oral epithelial cells (Figure 1A)
Summary
Head and neck cancer (HNC) is the sixth commonest cancer, with 90% of the histological type constituted by squamous cell carcinoma [1]. In contrast to Western countries, the oral cavity is the most frequent site of the primary lesion in Asian populations, possibly due to the stimulation of carcinogens, such as areca nut, alcohol and cigarettes [2]. The characteristics of oral squamous cell carcinoma (OSCC) differ markedly from SCC of other primary sites, including the potential association with human papillomavirus infection, aggressive tumor behavior, treatment resistance and poor disease-related survival [3,4,5,6]. Surgical resection is regarded as a curative treatment for cancer of the oral cavity, definitive concurrent chemoradiotherapy (CCRT) is the first-line treatment for inoperable locally advanced tumors. It is vital to identify prognostic biomarkers for risk stratification to guide further clinical management
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