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Role of Metastasis-Related Genes in Cisplatin Chemoresistance in Gastric Cancer.

ABSTRACT: The role of metastasis-related genes in cisplatin (CDDP) chemoresistance in gastric cancer is poorly understood. Here, we examined the expression of four metastasis-related genes (namely, c-met, HMGB1, RegIV, PCDHB9) in 39 cases of gastric cancer treated with neoadjuvant therapy with CDDP or CDDP+5-fluorouracil and evaluated its association with CDDP responsiveness. Comparison of CDDP-sensitive cases with CDDP-resistant cases, the expression of c-met, HMGB1, and PCDHB9 was correlated with CDDP resistance. Among them, the expression of HMGB1 showed the most significant correlation with CDDP resistance in multivariate analysis. Treatment of TMK-1 and MKN74 human gastric cancer cell lines with ethyl pyruvate (EP) or tanshinone IIA (TAN), which are reported to inhibit HMGB1 signaling, showed a 4-5-fold increase in inhibition by CDDP. Treatment with EP or TAN also suppressed the expression of TLR4 and MyD88 in the HMGB1 signal transduction pathway and suppressed the activity of NF?B in both cell lines. These results suggest that the expression of these cancer metastasis-related genes is also related to anticancer drug resistance and that suppression of HMGB1 may be particularly useful for CDDP sensitization.

SUBMITTER: Nishiguchi Y

PROVIDER: S-EPMC6981396 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Role of Metastasis-Related Genes in Cisplatin Chemoresistance in Gastric Cancer.

Nishiguchi Yukiko Y Oue Naohide N Fujiwara-Tani Rina R Sasaki Takamitsu T Ohmori Hitoshi H Kishi Shingo S Mori Shiori S Mori Takuya T Ikeda Naoya N Matsumoto Sohei S Wakatsuki Kohei K Luo Yi Y Yasui Wataru W Sho Masayuki M Kuniyasu Hiroki H

International journal of molecular sciences 20191230 1

The role of metastasis-related genes in cisplatin (CDDP) chemoresistance in gastric cancer is poorly understood. Here, we examined the expression of four metastasis-related genes (namely, c-met, HMGB1, RegIV, PCDHB9) in 39 cases of gastric cancer treated with neoadjuvant therapy with CDDP or CDDP+5-fluorouracil and evaluated its association with CDDP responsiveness. Comparison of CDDP-sensitive cases with CDDP-resistant cases, the expression of c-met, HMGB1, and PCDHB ...[more]

PMID: 31905926

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Project description:BackgroundWith the deepening research on fatty acid metabolism, people have achieved a preliminary understanding of it in the development and prognosis of tumors. However, few studies are still on the expression pattern and prognostic value of fatty acid metabolism-related genes in gastric cancer (GC).MethodsWe chose 93 genes relevant to fatty acid metabolism from the Gene Set Enrichment Analysis (GSEA) database. We analyzed differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA) patients. Univariate Cox analysis and LASSO regression were used to select the genes most related to prognosis and therefore developed a prognosis model. In addition, a dataset of 76 samples from Gene Expression Omnibus (GEO) selected as a test set to aid in the development of a prognostic model. The prognostic relevance of this model was confirmed using Kaplan-Meier survival analysis, univariate/multivariate Cox analysis, and receiver operating characteristic (ROC) curve. Finally, enrichment analysis and protein-protein interaction (PPI) were used to analyze the functional differences of patients with different risk. Immune infiltration analysis based on CIBERSORT could check the infiltration degree and immune function changes of immune cell subtypes in patients with different risk groups.ResultsOverexpression of ELOVL4, ADH4, CPT1C, and ADH1B was linked to poor overall survival (OS) in GC patients, according to our findings. Furthermore, according to prognostic factors, patients with lower risk score tend to have better prognosis than patients with higher risk score. In addition, we also found that the infiltration levels of B cells, dendritic cells, auxiliary T cells, mast cells, neutrophils and tumor-infiltrating lymphocytes in patients with high-risk group were significantly increased, and the type II IFN response of immune cells, CCR and MHC class I receptor functions were significantly enhanced, suggesting that the tumor microenvironment immune activity in patients with high-risk group was active.ConclusionsFour fatty acid metabolism-related genes were discovered to be closely connected to the prognosis of individuals with GC. Through analysis and verification, we believed that this prognostic model was reliable and instructive in the prediction of the prognosis of GC.

Dataset Information

Role of Metastasis-Related Genes in Cisplatin Chemoresistance in Gastric Cancer.

Publications

Role of Metastasis-Related Genes in Cisplatin Chemoresistance in Gastric Cancer.

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