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Gene regulatory network analysis with drug sensitivity reveals synergistic effects of combinatory chemotherapy in gastric cancer

 Jeong Hoon Lee  ;  Yu Rang Park  ;  Minsun Jung  ;  Sun Gyo Lim 
 SCIENTIFIC REPORTS, Vol.10(1) : 3932, 2020-03 
Journal Title
Issue Date
Aged ; Cell Movement / drug effects ; Cell Movement / genetics ; Cisplatin / therapeutic use ; Databases, Genetic ; Docetaxel / therapeutic use ; Drug Synergism ; Female ; Fluorouracil / therapeutic use ; Gene Regulatory Networks / genetics ; Gene Regulatory Networks / physiology ; Humans ; Male ; Middle Aged ; Stomach Neoplasms / drug therapy* ; Stomach Neoplasms / genetics ; Stomach Neoplasms / metabolism* ; Stomach Neoplasms / pathology
The combination of docetaxel, cisplatin, and fluorouracil (DCF) is highly synergistic in advanced gastric cancer. We aimed to explain these synergistic effects at the molecular level. Thus, we constructed a weighted correlation network using the differentially expressed genes between Stage I and IV gastric cancer based on The Cancer Genome Atlas (TCGA), and three modules were derived. Next, we investigated the correlation between the eigengene of the expression of the gene network modules and the chemotherapeutic drug response to DCF from the Genomics of Drug Sensitivity in Cancer (GDSC) database. The three modules were associated with functions related to cell migration, angiogenesis, and the immune response. The eigengenes of the three modules had a high correlation with DCF (-0.41, -0.40, and -0.15). The eigengenes of the three modules tended to increase as the stage increased. Advanced gastric cancer was affected by the interaction the among modules with three functions, namely cell migration, angiogenesis, and the immune response, all of which are related to metastasis. The weighted correlation network analysis model proved the complementary effects of DCF at the molecular level and thus, could be used as a unique methodology to determine the optimal combination of chemotherapy drugs for patients with gastric cancer.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Park, Yu Rang(박유랑) ORCID logo https://orcid.org/0000-0002-4210-2094
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