J Cancer 2018; 9(6):941-949. doi:10.7150/jca.23527

Research Paper

Epigenetic modification of SALL1 as a novel biomarker for the prognosis of early stage head and neck cancer

Kiyoshi Misawa1✉, Yuki Misawa1, Atsushi Imai1, Daiki Mochizuki1, Shiori Endo1, Masato Mima1, Ryuji Ishikawa1, Hideya Kawasaki2, Takashi Yamatodani1, Takeharu Kanazawa3

1. Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
2. Department of Regenerative & Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
3. Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan

Abstract

This study examined Sal-like protein (SALL)1 methylation profiles in head and neck squamous-cell carcinoma (HNSCC) patients at diagnosis and follow-up, and evaluated their prognostic significance and value as a biomarker. SALL1 expression was examined in a panel of cell lines by quantitative reverse transcription PCR (qRT-PCR). Promoter methylation was determined by quantitative methylation-specific polymerase chain reaction (qMSP) and was compared to the clinical characteristics of 205 samples. SALL1 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 31.7% of cases, with an odds ratio of 1.694 (95% confidence interval: 1.093-2.626; P = 0.018) by multivariate Cox proportional hazard regression analysis. SALL1 promoter hypermethylation showed highly discriminatory receiver operator characteristic curve profiles that clearly distinguished HNSCC from adjacent normal mucosal tissue, and was correlated with reduced disease-free survival in early stage T1 and T2 patients (log-rank test, P < 0.001). SALL1 methylation was significantly correlated with the methylation status of both SALL3 and CDH1. This study suggests that CpG hypermethylation is a likely mechanism of SALL1 gene inactivation, supporting the hypothesis that SALL1 might play a role in HNSCC tumorigenesis and could serve as an important biomarker.

Keywords: SALL1, methylation, early tumor stage patients, biomarker, HNSCC

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Misawa K, Misawa Y, Imai A, Mochizuki D, Endo S, Mima M, Ishikawa R, Kawasaki H, Yamatodani T, Kanazawa T. Epigenetic modification of SALL1 as a novel biomarker for the prognosis of early stage head and neck cancer. J Cancer 2018; 9(6):941-949. doi:10.7150/jca.23527. Available from http://www.jcancer.org/v09p0941.htm