SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer
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ORIGINAL ARTICLE
SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer Xiaoyang Xu1,2 · Xiaojing Chang3 · Yan Xu4 · Peng Deng1 · Jiang Wang2 · Chundong Zhang1 · Xinjiang Zhu1 · Shuchen Chen1 · Dongqiu Dai1 Received: 17 September 2019 / Accepted: 20 February 2020 © Japan Society of Clinical Oncology 2020
Abstract Background Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancerrelated mortality. In recent years, SAMD14 has been studied in various malignant cancers; however, little is known about the exact mechanisms of SAMD14 involvement in carcinogenesis and malignant progression. Methods 60 paired GC-normal gastric tissues were evaluated for their SAMD14 mRNA expression in relation to SAMD14 gene promoter methylation. GC patient survival was assessed by Kaplan–Meier analyses and a Cox’s proportional hazard model was employed for multivariate analyses. Results SAMD14 expression was significantly inversely correlated with the Borrmann type (P = 0.017), lymph node metastasis (P = 0.006) and tumor-node-metastasis (TNM) stage (P = 0.033). Methylation-specific PCR (MSP) revealed hypermethylation of the SAMD14 promoter in 56.7% (34/60) of the primary GC tissues tested and in 10% (6/60) of matched non-malignant tissues. The SAMD14 promoter methylation status was also related to pathological differentiation, Borrmann type, TNM stage and lymph node metastasis. The results showed SAMD14 expression was significantly downregulated in Borrmann type, lymph node metastasis and TNM stage, which showed significantly higher methylation. SAMD14 promoter hyper-methylation was significantly associated with a poor prognosis and could serve as an independent marker for survival using multivariate Cox regression analysis. Conclusions Our results indicated that promoter methylation was a key mechanism contributing to the downregulation of SAMD14 in GC. SAMD14 may be an epigenetically silenced tumor suppressor gene, and hyper-methylation of the SAMD14 promoter may serve as a biomarker to predict the clinical outcome of GC. Keywords Gastric cancer · SAMD14 gene · DNA methylation · Prognosis
Introduction
* Dongqiu Dai [email protected] 1
Department of Gastrointestinal Surgery and Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China
2
Department of Surgery, Fushun Mining Bureau General Hospital of Liaoning Health Industry Group (the Seventh Affiliated Hospital of China Medical University), Fushun, China
3
Department of Radiotherapy, The Second Hospital, Hebei Medical University, Shijiazhuang, China
4
The First Department of Radiotherapy, Fushun Fourth Hospital, Fushun, China
Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related mortality [1]. GC has a poor prognosis with a 5-year survival rate of 25–30% [2]. Currently, for patients with pT1stage GC, radical surgery (including endoscopic mucosal and submucosal dissec
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