Identification of Key Genes in Gastric Cancer by Bioinformatics Analysis

Chong, Xinyu; Peng, Rui; Sun, Yan; Zhang, Luyu; Zhang, Zheng

doi:10.1155/2020/7658230

Cited by 23 publications

(10 citation statements)

References 60 publications

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“…Among inflammatory pathways, we found also an overexpression of several genes identified as diagnostic or prognostic markers of gastric cancer including E2F1, that induces upregulation of lncRNA HCG18 thus stimulating proliferation and migration of gastric cancer ( 96 ), TIMP1, a key gene in the development of gastric cancer recognized as a potential prognostic marker when co-expressed with MMP-7 ( 97 , 98 ), S100A9, a diagnostic and prognostic biomarker in gastric cancer ( 99 , 100 ), and SERPINE1, highly expressed and significantly related to a poor prognosis of gastric adenocarcinoma ( 90 ). Interestingly, also LAMA5 that promotes colorectal liver metastasis growth, resulted upregulated in intestinal gastric cancer ( 101 ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

et al. 2021

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Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients’ prognosis, although CXCR2 is the only factor independently impacting overall survival.

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Section: Resultsmentioning

confidence: 99%

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

et al. 2021

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“…Among inflammatory pathways, we found also an overexpression of several genes identified as diagnostic or prognostic markers of gastric cancer including E2F1, that induces upregulation of lncRNA HCG18 thus stimulating proliferation and migration of gastric cancer [96], TIMP1, a key gene in the development of gastric cancer recognized as a potential prognostic marker when coexpressed with MMP-7 [97,98], S100A9, a diagnostic and prognostic biomarker in gastric cancer [99,100], and SERPINE1, highly expressed and significantly related to a poor prognosis of gastric adenocarcinoma [90]. Interestingly, also LAMA5 that promotes colorectal liver metastasis growth, resulted upregulated in intestinal gastric cancer [101].…”

Section: Resultsmentioning

confidence: 99%

Analysis of gastric cancer transcriptome allows the identification of histotype specific molecular signatures with prognostic potential

Carino

Graziosi

Marchianò

et al. 2021

Preprint

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Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2064 transcripts were differentially expressed between neoplastic and non neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histo-types of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients prognosis, although CXCR2 is the only factor independently impacting overall survival.

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“…The significance of the differentially expressed genes was identified based on the adjusted raw p-values to a false discovery rate (FDR) of < 0.05 and fold changes (log2 FC > 1). Gene ontology (GO, http://www.geneontology.org/ (accessed on 16 April 2021)) and Kyoto encyclopedia of genes and genomes (KEGG, http://www.genome.jp/kegg/analyses (accessed on 13 March 2021)) were explored to evaluate the biological function of the DEGs [71].…”

Section: Rna-seq Analysis Of Tumor Macrophagesmentioning

confidence: 99%

Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis

Qiao

Raju

Shyu

et al. 2021

IJMS

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Monocarboxylate transporter 2 (MCT2) is a major high-affinity pyruvate transporter encoded by the SLC16A7 gene, and is associated with glucose metabolism and cancer. Changes in the gut microbiota and host immune system are associated with many diseases, including cancer. Using conditionally expressed MCT2 in mice and the TC1 lung carcinoma model, we examined the effects of MCT2 on lung cancer tumor growth and local invasion, while also evaluating potential effects on fecal microbiome, plasma metabolome, and bulk RNA-sequencing of tumor macrophages. Conditional MCT2 mice were generated in our laboratory using MCT2loxP mouse intercrossed with mCre-Tg mouse to generate MCT2loxP/loxP; Cre+ mouse (MCT2 KO). Male MCT2 KO mice (8 weeks old) were treated with tamoxifen (0.18 mg/g BW) KO or vehicle (CO), and then injected with mouse lung carcinoma TC1 cells (10 × 105/mouse) in the left flank. Body weight, tumor size and weight, and local tumor invasion were assessed. Fecal DNA samples were extracted using PowerFecal kits and bacterial 16S rRNA amplicons were also performed. Fecal and plasma samples were used for GC−MS Polar, as well as non-targeted UHPLC-MS/MS, and tumor-associated macrophages (TAMs) were subjected to bulk RNAseq. Tamoxifen-treated MCT2 KO mice showed significantly higher tumor weight and size, as well as evidence of local invasion beyond the capsule compared with the controls. PCoA and hierarchical clustering analyses of the fecal and plasma metabolomics, as well as microbiota, revealed a distinct separation between the two groups. KO TAMs showed distinct metabolic pathways including the Acetyl-coA metabolic process, activation of immune response, b-cell activation and differentiation, cAMP-mediated signaling, glucose and glutamate processes, and T-cell differentiation and response to oxidative stress. Multi-Omic approaches reveal a substantial role for MCT2 in the host response to TC1 lung carcinoma that may involve alterations in the gut and systemic metabolome, along with TAM-related metabolic pathway. These findings provide initial opportunities for potential delineation of oncometabolic immunomodulatory therapeutic approaches.

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Identification of Key Genes in Gastric Cancer by Bioinformatics Analysis

Cited by 23 publications

References 60 publications

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

Analysis of gastric cancer transcriptome allows the identification of histotype specific molecular signatures with prognostic potential

Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis

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