SHISA3Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

Abstract

The purpose of this study was to evaluate the contribution of SHISA3 promoter methylation to laryngeal squamous cell carcinoma (LSCC). SHISA3 promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of the SHISA3 promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase in SHISA3 methylation in LSCC tissues compared with corresponding nontumor tissues (P = 4.58E − 12). The qRT-PCR results show a significant association between SHISA3 methylation and expression in LSCC (P = 1.67E − 03). In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest that SHISA3 promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rank P = 0.024; HR = 2.71; 95% CI = 1.024–7.177; P = 0.047). The results indicate that SHISA3 promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC.

The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma

“…Hypermethylation, causing the transcriptional silencing of the promoters of tumor suppressor genes (TSGs), occurs in various malignancies as part of the process of carcinogenesis . Compared with other molecular markers, DNA hypermethylation is a common and early event during the progression of various tumors and it is chemically and biologically more stable than RNA or the majority of proteins .…”

“…malignancies as part of the process of carcinogenesis. 34 Compared with other molecular markers, DNA hypermethylation is a common and early event during the progression of various tumors and it is chemically and biologically more stable than RNA or the majority of proteins. 35 Given these advantages and the development of technology for their detection, methylation biomarkers have great potential for use in early screening and diagnosis of cancer.…”

DNA methylation biomarkers for head and neck squamous cell carcinoma

“…In addition, the methylation profile of gene promoters was different for each type of tumor [46], suggesting that the detection of aberrant gene promoter methylation could serve as a potential molecular biomarker for tumors. The evaluation of methylation profiles as a tool for the diagnosis or prognosis of tumors has been described for many cancers, such as colorectal cancer [52], nasopharyngeal carcinoma [53], laryngeal squamous cell carcinoma [54], and HNSCC [55].…”

Elevated DNA methylation in malignant tumors of the sinonasal tract and its association with patient survival

“…Next promising biomarker is methylation of XRCC2 gene predicting the occurrence of late toxicity in radiotherapy-treated cervical cancer patients 18 . In head and neck cancer area methylation in PITX3, SHISA3 and FOXF2 in squamous cell types of carcinomas also represent promising prognostic biomarkers [19][20][21] . In our study we observed significantly higher methylation in three genes: GATA5, THBS1 and PAX5.…”