Molecular characteristics of gastric cancer with ERBB2 amplification

Dongyan Cao; Hongping Xu; Longteng Li; Zheng Ju; Baiqiang Zhai

doi:10.1016/j.heliyon.2023.e18654

Molecular characteristics of gastric cancer with ERBB2 amplification

Heliyon. 2023 Jul 25;9(8):e18654. doi: 10.1016/j.heliyon.2023.e18654. eCollection 2023 Aug.

Authors

Dongyan Cao^{1

2}, Hongping Xu², Longteng Li², Zheng Ju^{2

3}, Baiqiang Zhai²

Affiliations

¹ Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
² Henan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, China.
³ The Data Systems Department, 3D Medicines Inc., Shanghai, 201114, China.

Abstract

Gastric cancer is a prevalent malignancy with a high degree of heterogeneity, which has led to a poor therapeutic response. Though there are numerous HER2-targeted medicines for HER2+ gastric cancer, many trials have not indicated an improvement in overall survival. Here 29 ERBB2 amplification (ERBB2-Amp) type gastric cancer samples with WES and RNA-seq data were selected for investigation, which copy-number aberration (CNA) was +2. Initially, the somatic mutation and copy number variant (CNV) of them, which might cause resistance to HER2-targeted therapies, were systematically investigated evaluated, as well as their mutation signatures. Moreover, 37 modules were identified using weighted gene co-expression network analysis (WGCNA), including the blue module related to DFS status and lightcyan module correlated with ARHGAP26_ARHGAP6_CLDN18 rearrangement. In addition, focal adhesion and ECM-receptor interaction pathways were considerably enriched in the turquoise module with ERBB2 gene. ExportNetworkToCytoscape determined that MIEN1 and GRB7 are tightly connected to ERBB2., Finally, 14 single-cell intestinal gastric cancer samples were investigated, and it was shown that the TFAP2A transcription factor regulon was highly expressed in ERBB2^high group, as was the EMT score. Overall, our data provide comprehensive molecular characteristics of ERBB2-Amp type gastric cancer, which offers additional information to improve HER2-targeted gastric cancer treatment.

Keywords: EMT; ERBB2; Gastric cancer; HER2; WGCNA.