Abstract
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.
Highlights
The combination of docetaxel, cisplatin, and fluorouracil (DCF) is highly synergistic in advanced gastric cancer
Based on the function of each module and the sensitivity of each chemotherapeutic agent, here, our analysis enables us to explain the synergistic effects of DCF at the molecular level
We implemented an analysis pipeline to interpret the complementary effects of the drug combinations at the molecular level
Summary
The combination of docetaxel, cisplatin, and fluorouracil (DCF) is highly synergistic in advanced gastric cancer. 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 could be used as a unique methodology to determine the optimal combination of chemotherapy drugs for patients with gastric cancer. Its incidence is decreasing in some parts of the world, gastric cancer is still the fourth most common cancer worldwide[1,2] It poses a critical clinical challenge and is associated with poor prognosis, because a high percentage of patients are diagnosed at an advanced stage in some areas and due to its relatively chemoresistant properties and limited treatment options. If a methodology is identified to demonstrate the complementary effect of the DCF combination therapy, the candidates for a new drug combination may be indicated by the individual’s genetic profile
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