Dataset Information

Estimation of Hub Genes and Infiltrating Immune Cells in Non-Smoking Females with Lung Adenocarcinoma by Integrated Bioinformatic Analysis.

ABSTRACT: BACKGROUND In recent years, the morbidity and mortality rates of lung adenocarcinoma in non-smoking females have been increasing dramatically. Although much research has been done with some progress, the molecular mechanism remains unclear. In this study we aimed to estimate hub genes and infiltrating immune cells in non-smoking females with lung adenocarcinoma. MATERIAL AND METHODS Firstly, we obtained differentially expressed genes (DEGs) by GEO2R analysis based on 3 independent mRNA microarray datasets of GSE10072, GSE31547, and GSE32863. The DAVID database was utilized for functional enrichment analysis of DEGs. Moreover, we identified hub genes with prognostic value by STRING, Cytoscape, and Kaplan Meier plotter. Subsequently, these genes were further analyzed by Gene Expression Profiling Interactive Analysis, Oncomine, Tumor Immune Estimation Resource, and Human Protein Atlas. Finally, the immune infiltration analysis was performed by CIBERSORT and The Cancer Genome Atlas with R packages. RESULTS We found 315 DEGs enriching in the extracellular matrix organization, cell adhesion, integrin binding, angiogenesis, and hypoxic response. And among these DEGs, we identified 10 hub genes (SPP1, ENG, ATF3, TOP2A, COL1A1, PAICS, CAV1, CAT, TGFBR2, and ANGPT1) of significant prognostic value. Simultaneously, we illustrated the distribution and differential expressions of 22 immune cell subtypes. and dendritic cells resting and macrophages M1 were identified with prognostic significance. CONCLUSIONS The results indicated that 10 hub genes and 2 immune cell subtypes might be promising biomarkers for lung adenocarcinoma in non-smoking females. This finding needs to be further evaluated.

SUBMITTER: Li J

PROVIDER: S-EPMC7384333 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Estimation of Hub Genes and Infiltrating Immune Cells in Non-Smoking Females with Lung Adenocarcinoma by Integrated Bioinformatic Analysis.

Li Jie J Wang Ben B Li Xin X Zhu Yuxi Y

Medical science monitor : international medical journal of experimental and clinical research 20200716

BACKGROUND In recent years, the morbidity and mortality rates of lung adenocarcinoma in non-smoking females have been increasing dramatically. Although much research has been done with some progress, the molecular mechanism remains unclear. In this study we aimed to estimate hub genes and infiltrating immune cells in non-smoking females with lung adenocarcinoma. MATERIAL AND METHODS Firstly, we obtained differentially expressed genes (DEGs) by GEO2R analysis based on 3 independent mRNA microarra ...[more]

PMID: 32669531

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Project description:The present study aimed to explore important estrogen receptor-associated genes and to determine the potential pathogenic and prognostic factors for lung adenocarcinoma in non-smoking females. The gene expression profiles of the two datasets (GSE32863 and GSE75037) were downloaded from the Gene Expression Omnibus (GEO) database. Data for non-smoking female patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database were also downloaded. The Linear Models for Microarray Data package in R was used to explore the differentially expressed genes (DEGs) between samples from non-smoking female patients with lung adenocarcinoma and samples of adjacent non-cancerous lung tissue. The Database for Annotation, Visualization and Integrated Discovery was used for functional enrichment of the DEGs. The Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software were used to obtain a protein-protein interaction (PPI) network and to identify the hub genes. In addition, the network between the estrogen receptor and the DEGs was constructed. A Kaplan-Meier survival plot was used to analyze the overall survival (OS). In total, 248 DEGs were identified in the GEO database, and 2,362 DEGs were identified in TCGA database. The intersection of the two datasets (DEGs in GEO and TCGA) revealed 170 DEGs, and these were selected for further investigation. Gene Ontology was used to group the 170 DEGs into biological process, molecular function and cellular component categories. Kyoto Encyclopedia of Genes and Genomes pathway analysis was subsequently performed. A total of 27 hub genes, including caveolin 1 (CAV1), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1) and collagen type I ? 1 chain (COL1A1), were closely associated with the estrogen receptor. CAV1 and SPP1 were associated with the OS. However, MMP9 and COL1A1 did not have any significant effect on OS. In summary, the identification of CAV1, MMP9, SPP1 and COL1A1 may provide novel insights into the molecular mechanism of lung adenocarcinoma in non-smoking female patients, and the results obtained in the current study may guide future clinical studies.

Project description:The magnitude of the immune response is closely associated with clinical outcome in patients with cancer. However, finding potential therapeutic targets for lung cancer in the immune system remains challenging. Here, we constructed a vital immune-prognosis genes (VIPGs) based cluster of lung adenocarcinoma (LUAD) from IMMPORT databases and The Cancer Genome Atlas. A transcription factor regulatory network for the VIPGs was also established. The tumor microenvironment of LUAD was analyzed using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and single-sample Gene Set Enrichment Analysis. The immune checkpoints and genomic alterations were explored in the different immune clusters. We identified 15 VIPGs for patients with LUAD and clustered the patients into low-immunity and high-immunity subtypes. The immune score, stromal score and ESTIMATE score were significantly higher in the high-immunity subtype, whereas tumor purity was higher in the low-immunity subtype. In addition, the immune checkpoints cytotoxic T lymphocyte associate protein-4(CTLA4), programmed cell death protein-1 and programmed death-ligand were elevated in the low-immunity subtype. The genomic results also showed that the tumor mutation burden was higher in the high-immunity subtype. Finally, Gene Set Enrichment Analysis showed that several immune-related gene sets, including interleukin-2/STAT5 signaling, inflammatory response, interleukin-6/Janus kinase(JAK)/signal transducer and activator of transcription 3 (STAT3) signaling, interferon-gamma response and allograft rejection, were elevated in the high-immunity subtype. Finally, high-immunity patients exhibited greater overall and disease-specific survival outcome compared with low-immunity patients (log rank P = 0.013 and P = 0.0097). Altogether, here we have identified 15 immune-prognosis genes and a potential immune subtype for patients with LUAD, which may provide new insights into the prognosis and treatment of LUAD.

Project description:BackgroundPulmonary arterial hypertension (PAH) is a disease or pathophysiological syndrome which has a low survival rate with abnormally elevated pulmonary artery pressure caused by known or unknown reasons. In addition, the pathogenesis of PAH is not fully understood. Therefore, it has become an urgent matter to search for clinical molecular markers of PAH, study the pathogenesis of PAH, and contribute to the development of new science-based PAH diagnosis and targeted treatment methods.MethodsIn this study, the Gene Expression Omnibus (GEO) database was used to downloaded a microarray dataset about PAH, and the differentially expressed genes (DEGs) between PAH and normal control were screened out. Moreover, we performed the functional enrichment analyses and protein-protein interaction (PPI) network analyses of the DEGs. In addition, the prediction of miRNA and transcriptional factor (TF) of hub genes and construction miRNA-TF-hub gene network were performed. Besides, the ROC curve was used to evaluate the diagnostic value of hub genes. Finally, the potential drug targets for the 5 identified hub genes were screened out.Results69 DEGs were identified between PAH samples and normal samples. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in the inflammatory response and cytokine-cytokine receptor interaction, respectively. The miRNA-hub genes network was conducted subsequently with 131 miRNAs, 7 TFs, and 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) which screened out via constructing the PPI network. 17 drugs interacted with 5 hub genes were identified.ConclusionsThrough bioinformatic analysis of microarray data sets, 5 hub genes (CCL5, CXCL12, VCAM1, CXCR1, and SPP1) were identified from DEGs between control samples and PAH samples. Studies showed that the five hub genes might play an important role in the development of PAH. These 5 hub genes might be potential biomarkers for diagnosis or targets for the treatment of PAH. In addition, our work also indicated that paying more attention on studies based on these 5 hub genes might help to understand the molecular mechanism of the development of PAH.

Dataset Information

Estimation of Hub Genes and Infiltrating Immune Cells in Non-Smoking Females with Lung Adenocarcinoma by Integrated Bioinformatic Analysis.

Publications

Estimation of Hub Genes and Infiltrating Immune Cells in Non-Smoking Females with Lung Adenocarcinoma by Integrated Bioinformatic Analysis.

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