Promoter hypermethylation of SLIT2 is a risk factor and potential diagnostic biomarker for nasopharyngeal carcinoma

Abstract

SLIT2 is a candidate tumor suppressor gene and recent studies have shown that SLIT2 expression is suppressed or reduced by hypermethylation in the promoter region in various cancers. The aim of this study was to investigate the association between SLIT2 promoter methylation and nasopharyngeal carcinoma (NPC) and its relative diagnostic ability for NPC. Bisulfite pyrosequencing technology was performed to measure methylation levels of the SLIT2 promoter in tissue and plasma samples from 61 NPC patients and 38 normal volunteers. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic ability of SLIT2 methylation for diagnosing NPC. Our results showed that methylation levels of the SLIT2 promoter were significantly higher in NPC patients compared with individuals, both in tissue samples (P=2.57E−10) and plasma samples (plasma: P=3.86E−13). In addition, the frequency of SLIT2 promoter methylation markedly increased in the advanced stage (tissue: P=3.50E−05; plasma: P=1.14E−04) and advanced T classified (tissue: P=9.00E−06; plasma: P=3.80E−05), as well as in lymph node metastasis patients (tissue: P=1.82E−03; plasma: P=2.22E−03). In addition, the AUCs according to tissue and plasma samples were 0.846 and 0.866, respectively. When these two sample-types were combined, the AUC increased slightly to 0.874. Our study revealed that elevated SLIT2 promoter methylation contributed to the risk of NPC, as well as being involved in its progression and metastasis. Therefore, the methylated SLIT2 promoter could serve as a potential biomarker for diagnosing NPC.