人表皮生长因子受体2（）基因的扩增与中国胃癌患者的微卫星稳定状态相关。
Amplification of the human epidermal growth factor receptor 2 () gene is associated with a microsatellite stable status in Chinese gastric cancer patients.
作者信息
Huang He, Wang Zhengkun, Li Yi, Zhao Qun, Niu Zhaojian
机构信息
Department of Gastrointestinal Surgery, The First Hospital of Shanxi Medical University, Shanxi, China.
Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
出版信息
J Gastrointest Oncol. 2021 Apr;12(2):377-387. doi: 10.21037/jgo-21-47.
BACKGROUND
Gastric cancer (GC) is one of the most common cancers worldwide. However, little is known about the combination of HER2 amplification and microsatellite instability (MSI) status in GC. This study aimed to analyze the correlation of amplification with microsatellite instability (MSI) status, clinical characteristics, and the tumor mutational burden (TMB) of patients.
METHODS
A total of 192 gastric cancer (GC) patients were enrolled in this cohort. To analyze genomic alterations (GAs), deep sequencing was performed on 450 target cancer genes. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score.
RESULTS
The most frequently amplified genes in the GC patients included cyclin E1 (), human epidermal growth factor receptor 2 (), fibroblast growth factor receptor 2 (), cyclin D1 (), fibroblast growth factor 19 (), fibroblast growth factor 3 (), and fibroblast growth factor 4 (). The frequency of amplification was 9.38% (18/192). amplification was higher in females than in males (14.52% 6.92%, respectively, P=0.091), however, MSI was higher in males compared to females (7.69% 4.84%, respectively, P=0.46). amplification was higher in metastatic loci compared to primary lesions (23.08% 8.38%, respectively, P=0.079) and was lower in patients with high TMB (TMB-H) compared to those with low TMB (TMB-L) (4.0% 11.35%, respectively, P=0.12). While the frequency of MSI in metastatic foci was higher than that in primary lesions (15.38% 6.15%, respectively, P=0.48), MSI status was highly associated with TMB-H (20% 0%, respectively, P=3.66×10). Furthermore, amplification was negatively correlated with MSI status in Chinese GC patients.
CONCLUSIONS
amplification was negatively correlated with TMB-H and MSI status, and MSI status was significantly associated with TMB-H in Chinese GC patients. These data suggested that amplification might be a negative indicator for GC immunotherapy.
背景
胃癌（GC）是全球最常见的癌症之一。然而，关于胃癌中人类表皮生长因子受体2（HER2）扩增与微卫星不稳定性（MSI）状态的联合情况知之甚少。本研究旨在分析HER2扩增与微卫星不稳定性（MSI）状态、临床特征以及患者肿瘤突变负荷（TMB）之间的相关性。
方法
本队列共纳入192例胃癌（GC）患者。为分析基因组改变（GAs），对450个目标癌症基因进行了深度测序。通过内部算法测量TMB。基于MANTIS（正常-肿瘤不稳定性微卫星分析）评分推断MSI状态。
结果
GC患者中最常扩增的基因包括细胞周期蛋白E1（CCNE1）、人类表皮生长因子受体2（HER2）、成纤维细胞生长因子受体2（FGFR2）、细胞周期蛋白D1（CCND1）、成纤维细胞生长因子19（FGF19）、成纤维细胞生长因子3（FGF3）和成纤维细胞生长因子4（FGF4）。HER2扩增的频率为9.38%（18/192）。HER2扩增在女性中高于男性（分别为14.52%和6.92%，P = 0.091），然而，MSI在男性中高于女性（分别为7.69%和4.84%，P = 0.46）。HER2扩增在转移灶中高于原发灶（分别为
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