ABSTRACT

Objective: Associations between gene mutations and metastasis in gastric cancer (GC) remain contradictory, resulting in the inaccurate estimation of the magnitude of the risk associated with specific genotypes.

Methods: In this study, we first screened out four key driver genes (TP53, PIK3CA, APC and ARID1A) by jointly analyzing the mutation levels and searching the literature for genes associated with GC metastasis. We then performed a meta-analysis to demonstrate the relationship between these key driver gene mutations and GC metastasis, including lymphatic and distance metastasis.

Results: We found out four key driver genes (TP53, PIK3CA, APC and ARID1A), associated with risk of GC metastasis. The results showed that TP53 (OR 1.39, 95% CI 1.12–1.72) and APC mutations (OR 0.58, 95% CI 0.38–0.89) were associated with lymph node metastasis and distant metastasis in GC. And TP53 mutations (OR 1.65, 95% CI 1.25–2.18) were significantly related to GC metastasis in the Asian population. APC mutations (OR 0.54, 95% CI 0.29–1.00) were also related to GC metastasis in the European and American populations. There was no significant association with GC metastasis in PIK3CA or ARID1A mutations.

Expert opinion:Mutations of TP53 and APC play important roles in lymph node metastasis and distant metastasis of GC and may be potential important biomarkers of progression and therapeutic targets. These observations should be further prospectively verified.

摘要

目的: 胃癌 (GC) 中基因突变与转移之间的关联仍然存在矛盾，导致对与特定基因型相关风险大小的不准确估计。

方法：本研究首先通过联合分析突变水平和文献检索与GC转移相关的基因，筛选出4个关键驱动基因（TP53、PIK3CA、APC和ARID1A）。然后，我们进行了荟萃分析，以证明这些关键驱动基因突变与 GC 转移之间的关系，包括淋巴和远处转移。

结果：我们发现了四个与 GC 转移风险相关的关键驱动基因（TP53、PIK3CA、APC 和 ARID1A）。结果表明，TP53（OR 1.39, 95% CI 1.12-1.72）和APC突变（OR 0.58, 95% CI 0.38-0.89）与GC的淋巴结转移和远处转移有关。TP53 突变（OR 1.65, 95% CI 1.25-2.18）与亚洲人群的 GC 转移显着相关。APC 突变（OR 0.54, 95% CI 0.29-1.00）也与欧洲和美国人群的 GC 转移有关。PIK3CA 或 ARID1A 突变与 GC 转移没有显着相关性。

专家意见： TP53和APC的突变在GC的淋巴结转移和远处转移中起重要作用，可能是进展的潜在重要生物标志物和治疗靶点。这些观察结果应进一步进行前瞻性验证。