Abstract
Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia, and an unfavorable outcome is usually attributed to advanced stage NPC. Current methods for the early diagnosis of NPC have limitations in clinical practice. The aim of this study was to investigate the diagnostic ability of Septin 9 methylation for NPC. A quantitative methylation-sensitive PCR (qMS-PCR) assay was developed to measure the methylation status and levels of Septin 9 in nasopharyngeal tissues and paired swabs from patients with NPC, chronic nasopharyngitis, and healthy donors. Methylated Septin 9 was detected in 92% (23/25) of NPC tissues and 25% (4/16) of nasopharyngitis controls (p < 0.05). High-frequency hypermethylation with decreased mRNA expression of Septin 9 in NPC was also identified. Further, Septin 9 methylation was identified in 90.5% (19/21) of NPC biopsies and 71.4% (15/21) of paired swabs, indicating a good concordance between the two sample types. In addition, methylated Septin 9 was found in 16 (72.7%) nasal swabs from 22 NPC patients, 2 of 19 (10.5%) nasopharyngitis, but not in any of the healthy controls (p < 0.01). The methylation score in nasal swabs of the NPC group was also significantly higher than that of non-NPC controls (p < 0.001). Moreover, receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.882 of Septin 9 methylation tests to discriminate NPC from non-NPC subjects. Our study demonstrated that frequent methylation of Septin 9 was present in NPC. Its detection in nasopharyngeal swabs may provide a minimally invasive and informative method for identifying early NPC cases.
Highlights
Nasopharyngeal carcinoma (NPC) is a highly prevalent malignancy in Southeastern Asia and Southern China
Our results demonstrated that high frequency of Septin 9 methylation was present in NPC and its detection in nasopharyngeal swabs may be a minimally invasive tool for diagnosing NPC
We investigated the mRNA levels of Septin 9 between NPC and chronic nasopharyngitis by Quantitative Reverse Transcription PCR (qRT-PCR)
Summary
Nasopharyngeal carcinoma (NPC) is a highly prevalent malignancy in Southeastern Asia and Southern China. It is known as “Cantonese cancer” due to its unusually high incidence in Guangdong province, China. According to a recent report, about 60,000 Chinese were newly diagnosed with NPC in 2015 and 34,000 deaths from this disease [1]. Diagnosis of NPC mainly relies on clinical symptoms, imaging,immunological examinations, and histopathology. Nasopharyngeal tissues are Disease Markers taken under endoscopy from patients with suspected NPC and subjected to histological examination. It is invasive and multiple sampling may result in bleeding and other complications. It usually needs one week to finish the pathological diagnosis
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