Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma

Ratakorn Srisuttee,Areeya Arayataweegool,Patnarin Mahattanasakul,Somboon Keelawat,Apiwat Mutirangura,Nakarin Kitkumthorn,Napadon Tangjaturonrasme,Virachai Kerekhanjanarong

doi:10.1186/s12885-020-6692-z

Abstract

BackgroundOral squamous cell carcinoma (OSCC) is an aggressive human malignancy. Because of late diagnosis and recurrence of OSCC, the treatment of patients with OSCC is often ineffective. Thus, finding novel biomarkers of OSCC are essential. Here we derived a methylation marker by utilizing methylation microarray data and testing its capacity in cross-sectional study designed for OSCC detection and screening.MethodsAccording to bioinformatics analysis of total of 27,578 cg sites, cg22881914 of Nidogen 2 (NID2) methylation was selected for evaluation. Next, we confirmed the methylation status by bisulfite sequencing from the microdissected OSCC cells in comparison with the microdissected oral epithelia. Subsequently, we developed a simple technique using real-time PCR with the specific probe to examine the ability for the detection of OSCC in the oral epithelial samples, which included 103 oral rinse and 82 oral swab samples.ResultsBased on the comparison of microdissected tissue, cg22881914 of NID2 was proved to be methylated in most OSCC cells but unmethylated in the normal oral epithelia. Furthermore, the methylated NID2-relied quantitative PCR approach has demonstrated that this marker assists in distinguishing among patients with OSCC from normal oral epithelia, smokers, and patients with oral lichen planus using the non-invasive oral rinse and swab samples.ConclusionsSpecific methylation at cg22881914 of NID2 of OSCC could be used as an important potential marker for detecting OSCC. Thus, to certify the utility of this marker, further studies with a larger sample size are needed.

Highlights

Oral squamous cell carcinoma (OSCC) is an aggressive human malignancy
In our previous study using a methylation-specific database for OSCC, we revealed two methylated cg sites that can distinguish the differentiated OSCC from normal oral epithelia
To ensure the methylation at cg22881914 in Nidogen 2 (NID2) presented in OSCC cell, not in normal oral epithelial cell, manual

Summary

Introduction

Because of late diagnosis and recurrence of OSCC, the treatment of patients with OSCC is often ineffective. Oral cancer is a major health issue, with an incidence rate more than 280,000 patients, of which almost 50% died. The highest incidence rates of oral cancer for both men and women in general are noted in Southeast Asia and Central and Eastern Europe [4]. In patients with unresectable lesions, radiotherapy and chemotherapy would be a recommended treatment option for oral cancer, metastatic OSCC [7]. The possibility of using of target therapeutic approaches as essential treatment is difficult because of the low rate of successful investigations and high rate of mortality in recurrence cases [9].

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Conclusion