Abstract：
Gastric adenocarcinoma harbors a range of genetic and epigenetic alterations, including alterations in DNA copy number. However, the key genes that promote the development and progression of gastric adenocarcinoma remain unknown. To identify the key genes amplified in gastric adenocarcinoma, we performed array comparative genomic hybridization on formalin-fixed paraffin-embedded samples of surgically resected gastric adenocarcinoma. We detected a relatively wide genomic region of gain containing the vascular endothelial growth factor A (VEGFA) gene locus on chromosome 6p. VEGFA locus amplification in gastric adenocarcinoma was validated by fluorescence in situ hybridization. To assess the frequency of VEGFA locus amplification in gastric adenocarcinoma, we conducted multiplex ligation-dependent probe amplification (MLPA) assays using homemade probes designed to target the VEGFA gene locus. Eleven of 54 (20 %) gastric adenocarcinomas with MLPA values above 1.3 were defined as having VEGFA locus amplification. Next, we investigated the effect of VEGFA locus amplification on the clinicopathological characteristics of gastric adenocarcinomas and patient survival. VEGFA locus amplification demonstrated a significantly close relationship with pathological intestinal type and lower rates of venous invasion Furthermore, a Kaplan-Meier analysis showed that patients with VEGFA locus amplification had significantly better overall survival than those without amplification (p = 0.038), particularly in the long-term follow-up period. In conclusion, VEGFA locus amplification can predict modest aggressiveness and good outcomes, suggesting the possibility that it may predict a favorable prognosis in patients with gastric adenocarcinoma.
摘要：
胃腺癌具有一系列遗传和表观遗传改变，包括DNA拷贝数的改变.然而,促进胃腺癌发生发展的关键基因尚不清楚。为了确定胃腺癌中扩增的关键基因，我们对经手术切除的胃腺癌的福尔马林固定石蜡包埋样本进行了阵列比较基因组杂交.我们在6p染色体上检测到一个相对较宽的增益基因组区域，其中包含血管内皮生长因子A（VEGFA）基因座。通过荧光原位杂交验证了胃腺癌中VEGFA基因座的扩增。为了评估胃腺癌中VEGFA基因座扩增的频率，我们使用旨在靶向VEGFA基因位点的自制探针进行多重连接依赖性探针扩增(MLPA)测定.MLPA值高于1.3的54例（20％）胃腺癌中的11例被定义为具有VEGFA基因座扩增。接下来,我们研究了VEGFA基因扩增对胃腺癌临床病理特征和患者生存的影响.VEGFA基因座扩增显示与病理性肠型和较低的静脉浸润率密切相关。Kaplan-Meier分析显示，VEGFA基因座扩增患者的总生存期明显优于未扩增患者（p=0.038），特别是在长期随访期间。总之,VEGFA基因座扩增可以预测适度的侵袭性和良好的结果，提示它可能预测胃腺癌患者的良好预后。
