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SAMD14 promoter methylation is strongly associated with gene expression and poor prognosis in gastric cancer.
International Journal of Clinical Oncology ( IF 2.4 ) Pub Date : 2020-03-21 , DOI: 10.1007/s10147-020-01647-4
Xiaoyang Xu 1, 2 , Xiaojing Chang 3 , Yan Xu 4 , Peng Deng 1 , Jiang Wang 2 , Chundong Zhang 1 , Xinjiang Zhu 1 , Shuchen Chen 1 , Dongqiu Dai 1
Affiliation  

Abstract

Background

Gastric cancer (GC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related 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 hyper-methylation 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.



中文翻译:

SAMD14 启动子甲基化与胃癌的基因表达和不良预后密切相关。

摘要

背景

胃癌 (GC) 是全球第五大最常见的恶性肿瘤,也是癌症相关死亡的第三大原因。近年来,SAMD14在多种恶性肿瘤中得到了研究;然而,关于SAMD14参与致癌和恶性进展的确切机制知之甚少

方法

评估了 60 对 GC-正常胃组织与 SAMD14 基因启动子甲基化相关的 SAMD14 mRNA 表达。GC 患者存活率通过 Kaplan-Meier 分析评估,Cox 比例风险模型用于多变量分析。

结果

SAMD14表达与Borrmann型(P  = 0.017)、淋巴结转移(P  = 0.006)和肿瘤淋巴结转移(TNM)分期(P  = 0.033)呈显着负相关。甲基化特异性 PCR (MSP) 显示SAMD14启动子在 56.7% (34/60) 测试的原发 GC 组织和 10% (6/60) 匹配的非恶性组织中发生超甲基化。所述SAMD14启动子甲基化状态也与病理分化,Borrmann分型,TNM分期和淋巴结转移。结果显示SAMD14表达在Borrmann型、淋巴结转移和TNM分期显着下调,甲基化程度显着升高。SAMD14启动子高甲基化与不良预后显着相关,使用多变量 Cox 回归分析可作为生存的独立标志物。

结论

我们的结果表明启动子甲基化是导致GC中SAMD14下调的关键机制。SAMD14可能是一种表观遗传沉默的肿瘤抑制基因,SAMD14启动子的超甲基化可能作为预测 GC 临床结果的生物标志物。

更新日期:2020-03-24
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