Molecular characteristics of gastric cancer with ERBB2 amplification
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 (ERBB...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023058620 |
| _version_ | 1797733004036014080 |
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| author | Dongyan Cao Hongping Xu Longteng Li Zheng Ju Baiqiang Zhai |
| author_facet | Dongyan Cao Hongping Xu Longteng Li Zheng Ju Baiqiang Zhai |
| author_sort | Dongyan Cao |
| collection | DOAJ |
| description | 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 ERBB2high 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. |
| first_indexed | 2024-03-12T12:21:45Z |
| format | Article |
| id | doaj.art-8579dd522a9f4833a6725529de3569c2 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T12:21:45Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8579dd522a9f4833a6725529de3569c22023-08-30T05:52:06ZengElsevierHeliyon2405-84402023-08-0198e18654Molecular characteristics of gastric cancer with ERBB2 amplificationDongyan Cao0Hongping Xu1Longteng Li2Zheng Ju3Baiqiang Zhai4Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China; Henan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, ChinaHenan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, ChinaHenan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, ChinaHenan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, China; The Data Systems Department, 3D Medicines Inc., Shanghai, 201114, China; Corresponding author. Henan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, China.Henan Railway Food Safety Management Engineering Technology Research Center, Zhengzhou Railway Vocational & Technology College, Zhengzhou, 451460, China; Corresponding author.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 ERBB2high 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.http://www.sciencedirect.com/science/article/pii/S2405844023058620Gastric cancerERBB2HER2WGCNAEMT |
| spellingShingle | Dongyan Cao Hongping Xu Longteng Li Zheng Ju Baiqiang Zhai Molecular characteristics of gastric cancer with ERBB2 amplification Heliyon Gastric cancer ERBB2 HER2 WGCNA EMT |
| title | Molecular characteristics of gastric cancer with ERBB2 amplification |
| title_full | Molecular characteristics of gastric cancer with ERBB2 amplification |
| title_fullStr | Molecular characteristics of gastric cancer with ERBB2 amplification |
| title_full_unstemmed | Molecular characteristics of gastric cancer with ERBB2 amplification |
| title_short | Molecular characteristics of gastric cancer with ERBB2 amplification |
| title_sort | molecular characteristics of gastric cancer with erbb2 amplification |
| topic | Gastric cancer ERBB2 HER2 WGCNA EMT |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023058620 |
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