SSTR2 promoter hypermethylation is associated with the risk and progression of laryngeal squamous cell carcinoma in male

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SSTR2 promoter hypermethylation is associated with the risk and progression of laryngeal squamous cell carcinoma in males Zhisen Shen1*, Xiaoying Chen2, Qun Li1,2, Chongchang Zhou1,2, Jinyun Li2, Huadan Ye2 and Shiwei Duan2*

Abstract Background: Somatostatin receptor 2 (SSTR2) encodes somatostatin receptor that can inhibit the cell proliferation of solid tumors. Promoter hypermethylation is likely to silence the expression of SSTR2. The goal of our study was to investigate the association between SSTR2 promoter methylation and the risk and progression of laryngeal carcinoma. Methods: In the current study, tumor tissues and their adjacent non-tumor tissues were collected from a total of 87 laryngeal squamous cell carcinoma (LSCC) male patients. DNA methylation levels of nine SSTR2 promoter CpGs were measured using the bisulphite pyrosequencing technology. Results: Our results revealed that there was a significantly increased SSTR2 promoter methylation in LSCC tissues than in their adjacent non-cancerous tissues (adjusted P = 0.003). Breakdown analysis by age indicated that the significant association was mainly contributed by patients younger than 60 (adjusted P = 0.039) but not in patients older than 60. Meanwhile, the significant association was observed in the patients with moderately (adjusted P = 0.037) and well differentiated tissues (adjusted P = 0.028), as well as the patients with histological stage IV (adjusted P = 0.031). Multivariate Cox analysis suggested that SSTR2 promoter methylation was an independent prognostic factor of LSCC (HR = 1.127, 95 % CI = 1.034–1.228). Conclusions: In conclusion, SSTR2 promoter hypermethylation might be associated with the risk and progression of LSCC in males. Keywords: Laryngeal carcinoma, SSTR2, DNA methylation, Male

Background Laryngeal cancer is a devastating malignancy of head and neck, and its incidence and mortality rates are increasing recently [1]. Despite improvement of oncological and surgical treatments over the last 20 years, 5year survival rates of laryngeal cancer remained poor since the middle of 1980s [2, 3]. More than 90 % of laryngeal cancer has been pathologically identified as laryngeal squamous cell carcinoma (LSCC) [1]. According * Correspondence: [email protected]; [email protected] Zhisen Shen and Xiaoying Chen are co-first authors of this work. 1 Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315040, China 2 Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China

to the Cancer Facts & Figures 2015 data, the majority of laryngeal cancer patients are males. Currently, total laryngectomy and postoperative radiotherapy are the most common treatments for LSCC [4]. Due to serious impairment in laryngeal function and low quality life that brings for patients, the exact molecular pathogenesis of LSCC is still urgently needed to be explored. It is hypothesized that LSCC may result from the in