Prognosis genes in gastric adenocarcinoma identified by cross talk genes in disease-related pathways

Abstract

The aim of the present study was to investigate the prognostic value of genes that participate in the development of gastric adenocarcinoma, via exploring gene cross talk in disease-related pathways. Differentially expressed genes (DEGs) in the gastric samples were identified by analyzing the expression data downloaded from the GEO database. The DEGs were subjected to the human protein-protein interaction (PPI) network to construct the PPI network of DEGs, which was then used for the identification of key genes in cancer samples via the expression deviation score and degree in the network. A total of 635 DEGs, including 432 downregulated and 203 upregulated ones were screened in the gastric adenocarcinomas samples. The PPI network of DEGs comprised 590 DEGs and 4,299 interaction pairs. A total of 200 key genes were obtained, which were significantly enriched in six downregulated and six upregulated pathways. Cross talk genes in the connected pathways were analyzed, and the Kyoto Encyclopedia of Genes and Genomes pathways hsa00980 (Metabolism of xenobiotics by cytochrome P450) and hsa00982 (Drug metabolism) were reported to share 8 cross talk genes: ADH7, ALDH3A1, GSTA1, GSTA2, UGT2B17, UGT2B10, ADH1B and CYP2C18. Among all cross talk genes, ADH7, ALDH3A1 and CLDN3 were the most specific genes. The high- and low-risk samples identified by the prognosis model presented a remarkable difference in total survival time, indicating its robustness and sensitivity as the prognosis genes for gastric adenocarcinoma. ADH7, ALDH3A1, GSTA1, GSTA2, UGT2B17, UGT2B10, ADH1B, CYP2C18ADH7, ALDH3A1 and CLDN3 may be used as the prognosis markers and target biomarkers for chemotherapies in gastric adenocarcinoma.

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

“…Consistent with preceding studies, we demonstrated that ALDH3A1 displayed a high expression level in metastasis colon cancer cells compared with primary colon cancer cells and provided potential biomarkers to develop new therapy to target stem cell caused metastasis [22]. ALDH3A1 was also screened in gastric adenocarcinoma to be used as the prognosis marker [23]. Although ALDH3A1 was screened and presented a predictive role for tumor progression in different cancers, few studies identified this phenomenon.…”

“…Our study demonstrated that ALDH3A1 in LUAD tumor samples of patients with M1 was significantly upregulated than in patients with M0. Accumulating evidence demonstrated that ALDH3A1 could influence tumor cell proliferation [23][24][25][26]. We, therefore, explored the potential role of ALDH3A1 in mediating cancer cell proliferation.…”

An advanced network pharmacology study to explore the novel molecular mechanism of Compound Kushen Injection for treating hepatocellular carcinoma by bioinformatics and experimental verification

“…Most of the drugs are metabolized in the liver by drug-metabolizing enzymes, and the primary drug-metabolizing enzymes are severely dysregulated in HCC, leading to chemotherapy failur e[ 98 ]. Moreover, dysfunction of the drug metabolism-cytochrome P450 pathway (hsa00982) has been reported to induce drug resistance or adverse reactions during chemotherapy in cancer by interrupting drug metabolism and promoting drug excretion [ 99 ]. Arachidonic acid metabolism has been proved to significantly impact the occurrence and development of various malignant diseases [ 100 ].…”

Nuclear Factor Erythroid 2–Related Factor 2 Depletion Sensitizes Pancreatic Cancer Cells to Gemcitabine via Aldehyde Dehydrogenase 3a1 Repression

“…The expression levels of ALDH3A1 in surgically resected cancer tissues correlate with the prognosis of patients with gastric cancer. Combined with other differentially expressed genes, ALDH3A1 shows diagnostic efficacy in patients with gastric cancer (Zhao et al, 2017). The impact of ALDH3A1 expression status on the prognosis of pancreatic cancers needs further validation in relationship with therapeutic intervention such as adjuvant chemotherapy.…”