The impact of ADAMTS14 genetic polymorphisms and its function on susceptibility to and prognosis of gastric cancer in a Chinese Han population.

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastric Cancer Pub Date : 2025-05-01 Epub Date: 2025-02-24 DOI:10.1007/s10120-025-01598-7

Pengyu Li, Jiacheng Dong, Yuan Li, Jiang Yan, Jiawei Wang, Shuqing Cao, Wei Cao, Xinyu Zhao, Ao Xue, Zekuan Xu, Li Yang

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引用次数: 0

Abstract

Background: Single nucleotide polymorphisms (SNPs) are associated with various diseases, including gastric cancer. The ADAMTS14 gene is linked to multiple types of cancer. However, the relationship between ADAMTS14 and its genetic polymorphisms with susceptibility to gastric cancer (GC) and prognosis remains unclear.

Methods: A case-control study was conducted involving 855 patients diagnosed with gastric cancer (GC) and an equal number of cancer-free controls. Following rigorous statistical analysis, molecular experiments were performed to elucidate the functional significance of the SNPs in the context of GC.

Results: ADAMTS14 rs3740440 (OR = 1.45, p = 0.014) shows a significant association with increased GC risk, while rs11572 (OR = 0.42, p < 0.001) is associated with protection against GC. Moreover, patients with the (CG + GG) genotype of rs3740440 exhibit a poor prognosis (HR = 1.68, p = 0.007). Mechanistically, luciferase reporter assays revealed that the G allele of rs3740440 disrupts the binding of hsa-miR-4294 and hsa-miR-3198 to the 3' untranslated region (3' UTR) of ADAMTS14, leading to increased expression of ADAMTS14 and the promotion of malignant behaviors in GC cells.

Conclusions: Our findings underscore the significant role of ADAMTS14 SNPs in both the risk and prognosis of gastric cancer (GC), providing valuable insights into the underlying molecular mechanisms. Specifically, rs3740440 disrupts the interaction between ADAMTS14 and miRNA, resulting in increased expression of ADAMTS14. This heightened expression enhances its malignant biologic behaviors, indicating that rs3740440 could be a potential predictive marker for gastric cancer risk and prognosis.

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ADAMTS14基因多态性及其功能对中国汉族人群胃癌易感性和预后的影响

背景：单核苷酸多态性（snp）与多种疾病有关，包括胃癌。ADAMTS14基因与多种类型的癌症有关。然而，ADAMTS14及其遗传多态性与胃癌易感性和预后的关系尚不清楚。方法：采用病例对照研究，纳入855例胃癌（GC）患者和同等数量的无癌对照。经过严格的统计分析，我们进行了分子实验来阐明snp在GC背景下的功能意义。结果：ADAMTS14 rs3740440 （OR = 1.45, p = 0.014）与胃癌风险增加显著相关，而rs11572 （OR = 0.42, p）与胃癌风险增加显著相关。结论：我们的发现强调了ADAMTS14 snp在胃癌（GC）风险和预后中的重要作用，为潜在的分子机制提供了有价值的见解。具体来说，rs3740440破坏了ADAMTS14与miRNA之间的相互作用，导致ADAMTS14的表达增加。这种高表达增强了其恶性生物学行为，提示rs3740440可能是胃癌风险和预后的潜在预测标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.