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伴有扩增的胃癌的分子特征

Molecular characteristics of gastric cancer with amplification.

作者信息

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

机构信息

Shanghai 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, China.

出版信息

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

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 amplification (-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 __ rearrangement. In addition, focal adhesion and ECM-receptor interaction pathways were considerably enriched in the turquoise module with gene. ExportNetworkToCytoscape determined that and are tightly connected to ., Finally, 14 single-cell intestinal gastric cancer samples were investigated, and it was shown that the transcription factor regulon was highly expressed in group, as was the EMT score. Overall, our data provide comprehensive molecular characteristics of -Amp type gastric cancer, which offers additional information to improve HER2-targeted gastric cancer treatment.

摘要

胃癌是一种普遍存在且具有高度异质性的恶性肿瘤,这导致了较差的治疗反应。尽管有许多针对HER2阳性胃癌的HER2靶向药物,但许多试验并未显示总生存期有所改善。在此,选择了29个具有全外显子组测序(WES)和RNA测序(RNA-seq)数据的扩增(-Amp)型胃癌样本进行研究,其拷贝数变异(CNA)为+2。首先,系统地研究和评估了它们可能导致对HER2靶向治疗产生耐药性的体细胞突变和拷贝数变异(CNV),以及它们的突变特征。此外,使用加权基因共表达网络分析(WGCNA)鉴定了37个模块,包括与无病生存期(DFS)状态相关的蓝色模块和与__重排相关的浅青色模块。此外,粘着斑和细胞外基质-受体相互作用途径在具有基因的绿松石模块中显著富集。ExportNetworkToCytoscape确定__和__与__紧密相连。最后,研究了14个单细胞肠型胃癌样本,结果表明__转录因子调控子在__组中高表达,上皮-间质转化(EMT)评分也是如此。总体而言,我们的数据提供了-Amp型胃癌的全面分子特征,为改善HER2靶向胃癌治疗提供了更多信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/054e/10405018/a68b6ffdfb15/gr1.jpg

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