Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

Mao, Deli; Xu, Rui; Chen, Hengxing; Chen, Xiancong; Li, Dongsheng; Song, Shenglei; Wei, Zhewei; Zhang, Changhua

doi:10.3389/fcell.2021.716461

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…ECM-receptor interaction pathway is identified as an important pathway associated with the progression of GC ( Hu and Chen, 2012 ). Focal adhesion plays a key role in regulating cell survival, and proliferation, migration, and invasion of GC cells ( Mao et al, 2021 ). The PI3K-Akt signaling pathway plays an important role in the development and progression of GC ( Matsuoka and Yashiro, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis

Hossain

Reza

et al. 2022

Front. Mol. Biosci.

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Gastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don’t have the 5′-3′ polarity and a 3′ polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.

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Section: Discussionmentioning

confidence: 99%

Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis

Hossain

Reza

et al. 2022

Front. Mol. Biosci.

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“…Consistent with the above conclusions, the results of enrichment analysis, such as response to hypoxia and decreased oxygen, and HIF-1 signaling pathway, indicated that this module's key metabolic genes had tight association with hypoxia process. Previous studies have demonstrated that focal adhesions, as mediators of tumor cells and the extracellular matrix, are vital in various ways within tumor migration, invasion, and drug resistance (35). The results of GO enrichment analysis, such as focal adhesion and cell-substrate junction, indicated that the key metabolic genes in the module may be closely associated with metastasis.…”

Section: Discussionmentioning

confidence: 98%

Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma

Yan²,

Peng³

et al. 2022

Front. Immunol.

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BackgroundGlycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients.MethodsGene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation.ResultsThrough bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration.ConclusionTherefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.

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“…ECM-receptor interaction was reported as an important pathway linked with the progression of GC [60] . Focal adhesion was identified as a key player in regulating cell survival and proliferation, migration, and invasion of GC cells [61] . The PI3K-Akt signaling pathway was known to play an important role in the development and progression of GC [62] .…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes as Potential Drug Targets for Gastric Cancer

Hossain

Reza

Peng

et al. 2023

Tsinghua Sci. Technol.

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Gastric cancer (GC) is one of the most common cancers and ranks the third in cancer mortality all over the world. The goal of this study was to identify potential hub-genes, highlighting their functions, signaling pathways, and candidate drugs for the treatment of GC patients. We used publicly available next generation sequencing (NGS) data to identify differentially expressed (DE) genes. The top DE genes were mapped to STRING database to construct the protein-protein interaction (PPI) network and top hub genes were selected for further analysis. We found a total of 1555 DE genes with 870 upregulated and 685 downregulated genes in GC. We selected the top 400 (200 upregulated and 200 downregulated) genes to construct a PPI network and extracted the top 15 hub genes. The gene ontology (GO) term and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of the 15 hub genes exposed some important functions and signaling pathways that were significantly associated with GC patients. The survival analysis of the hub genes disclosed that the lower expressions of the three hub genes CDH2, COL4A1, and COL5A2 were associated with better survival of GC patients. These three genes might be the candidate biomarkers for the diagnosis and treatment of GC. Then, we considered 3 key proteins (genomic biomarkers) (COL4A1, CDH2, and CO5A2) as the drug target proteins (receptors), performed their docking analysis with the 102 meta-drug agents, and found Everolimus, Docetaxel, Lanreotide, Venetoclax, Temsirolimus, and Nilotinib as the top ranked 6 candidate drugs with respect to our proposed target proteins for the treatment against GC patients. Therefore, the proposed drugs might play vital role for the treatment against GC patients.

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Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

Cited by 15 publications

References 52 publications

Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis

Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis

Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma

Identification of Key Genes as Potential Drug Targets for Gastric Cancer

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