scholarly journals Predictive Value of CCNB1, BUB1B and TTK in the Progression and Prognosis of Lung Adenocarcinoma

2020 ◽  
Author(s):  
Lecai Xiong ◽  
Yuquan Bai ◽  
Minglin Zhu ◽  
Zetian Yang ◽  
Jinping Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Lung Cancer Patients

Lung cancer predominates in cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) being a common histological subtype of lung cancer. The aim at this study was to search for biomarkers associated with the progression and prognosis of LUAD. We have integrated the expression profiles of 1174 lung cancer patients from five GEO datasets (GSE18842, GSE19804, GSE30219, GSE40791 and GSE68465) and identified a set of differentially expressed genes. Functional enrichment analysis showed that these genes are closely related to the progression of LUAD, such as cell cycle, mitosis and adhesion. Cytoscape software was used to establish a protein-protein interaction (PPI) network to analyze important modules using Molecular Complex Detection (MCODE), and finally CCNB1, BUB1B and TTK were selected for further study. The study found that compared with non-tumor lung tissue, CCNB1, BUB1B and TTK are highly expressed in LUAD. Kaplan-Meier analysis showed that CCNB1, BUB1B and TTK were negatively correlated with the overall survival and disease-free survival of patients. Gene set enrichment analysis (GSEA) demonstrated that for the samples of any hub gene highly expressed, most of the functional gene sets enriched in cell cycle. In summary, CCNB1, BUB1B and TTK can be used as biomarkers of poor prognosis of LUAD. The high expression of CCNB1, BUB1B and TTK can accelerate the progression of LUAD and lead to shorter survival, suggesting that they may be potential targets for treatment in LUAD.

scholarly journals Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Xiang Qian ◽  
Zhuo Chen ◽  
Sha Sha Chen ◽  
Lu Ming Liu ◽  
Ai Qin Zhang
Keyword(s):  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Ductal Adenocarcinoma ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Kaplan Meier ◽  
Human Protein Atlas

The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

scholarly journals Improved cancer biomarkers identification using network-constrained infinite latent feature selection

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246668
Author(s):  
Lihua Cai ◽  
Honglong Wu ◽  
Ke Zhou
Keyword(s):  
Feature Selection ◽  
Expression Profiles ◽  
Biological Significance ◽  
Feature Selection Method ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Gene Sets ◽  
Significant Gene

Identifying biomarkers that are associated with different types of cancer is an important goal in the field of bioinformatics. Different researcher groups have analyzed the expression profiles of many genes and found some certain genetic patterns that can promote the improvement of targeted therapies, but the significance of some genes is still ambiguous. More reliable and effective biomarkers identification methods are then needed to detect candidate cancer-related genes. In this paper, we proposed a novel method that combines the infinite latent feature selection (ILFS) method with the functional interaction (FIs) network to rank the biomarkers. We applied the proposed method to the expression data of five cancer types. The experiments indicated that our network-constrained ILFS (NCILFS) provides an improved prediction of the diagnosis of the samples and locates many more known oncogenes than the original ILFS and some other existing methods. We also performed functional enrichment analysis by inspecting the over-represented gene ontology (GO) biological process (BP) terms and applying the gene set enrichment analysis (GSEA) method on selected biomarkers for each feature selection method. The enrichments analysis reports show that our network-constraint ILFS can produce more biologically significant gene sets than other methods. The results suggest that network-constrained ILFS can identify cancer-related genes with a higher discriminative power and biological significance.

scholarly journals Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huan Deng ◽  
Qingqing Hang ◽  
Dijian Shen ◽  
Yibi Zhang ◽  
Ming Chen
Keyword(s):  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Prognostic Indicators ◽  
Hub Genes ◽  
Coexpressed Genes

Abstract Purpose Exploring the molecular mechanisms of lung adenocarcinoma (LUAD) is beneficial for developing new therapeutic strategies and predicting prognosis. This study was performed to select core genes related to LUAD and to analyze their prognostic value. Methods Microarray datasets from the GEO (GSE75037) and TCGA-LUAD datasets were analyzed to identify differentially coexpressed genes in LUAD using weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. Functional enrichment analysis was conducted, and a protein–protein interaction (PPI) network was established. Subsequently, hub genes were identified using the CytoHubba plug-in. Overall survival (OS) analyses of hub genes were performed. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (THPA) databases were used to validate our findings. Gene set enrichment analysis (GSEA) of survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings. Results We identified 486 differentially coexpressed genes. Functional enrichment analysis suggested these genes were primarily enriched in the regulation of epithelial cell proliferation, collagen-containing extracellular matrix, transforming growth factor beta binding, and signaling pathways regulating the pluripotency of stem cells. Ten hub genes were detected using the maximal clique centrality (MCC) algorithm, and four genes were closely associated with OS. The CPTAC and THPA databases revealed that CHRDL1 and SPARCL1 were downregulated at the mRNA and protein expression levels in LUAD, whereas SPP1 was upregulated. GSEA demonstrated that DNA-dependent DNA replication and catalytic activity acting on RNA were correlated with CHRDL1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 were significantly downregulated in LUAD. Conclusions Our study revealed that survival-related hub genes closely correlated with the initiation and progression of LUAD. Furthermore, CHRDL1 and SPARCL1 are potential therapeutic and prognostic indicators of LUAD.

scholarly journals Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

2021 ◽  
Author(s):  
Liang Chen ◽  
Liulin Xiong ◽  
Weinan Chen ◽  
Lizhe An ◽  
Huanrui Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Biomarkers

Abstract Background Bladder cancer (BLCA) is one of most common urinary tract malignant tumor and immunotherapy have generated a great deal of interest in BLCA. Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of BLCA. Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Objective In this study, we aimed to investigate the role of mutations genes and subtypes in prognosis and immune checkpoint prediction in BLCA. Method Mutation information and expression profiles were acquired from The Cancer Genome Atlas (TCGA) database. Integrated bioinformatics analysis was carried out to explore the mutation genes of BLCA. Functional enrichment analysis Gene Ontology (GO) and Gene set enrichment analysis (GSEA) was conducted. The infiltrating immune cells and the prediction of ICB between different subtypes group were explored using immuCellAI algorithm. Results The mutation genes Filaggrin (FLG) gene were identified. Following the study on its subtypes and functional enrichment analysis, Sub2 of FLG-wide type was found to have relationships with poor prognosis and immune infiltration BLCA. What’s more, Sub2 of FLG-wide type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. Conclusion This research provides a new basis and ideas for guiding the clinical application of BLCA immunotherapy.

scholarly journals Identification of key prognosis-associated genes in the lung adenocarcinoma

2020 ◽  
Author(s):  
HongBo Ma ◽  
XiaoLi Wu ◽  
MiaoMiao Tao ◽  
Uthaman Jithin ◽  
GenDou Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Prognostic Biomarkers ◽  
Key Genes ◽  
The Impact

Abstract Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death globally, and lung adenocarcinoma (LUAD) accounts for almost 40% of all lung cancer cases. In recent years, despite better understanding of the pathogenesis of the disease and achievements in the multimodal treatment of tumors, there is an urgent need to identify new diagnostic and prognostic biomarkers In this study, we aim to identify the potential key genes related to the pathogenesis and prognosis of LUAD by using comprehensive bioinformatics analysis. The gene expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, and we calculated the LUAD immune scores and stromal scores by using the ESTIMATE algorithm. Based on these scores, we further quantified the immune and stromal components and obtained the differentially expressed genes (DEGs) in the tumor. Overall survival analysis could better reflect the impact of genes related to immune and stromal cells on the prognosis. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted, while protein-protein interaction (PPI) network was obtained from STRING. Analysis of the correlation revealed that these genes are mainly involved in the immune/inflammatory response. In conclusion, our study showed that 11 prognostic genes (CD33, IRF8, CD80, CD53, IL16, LY86, CD79B, TYROBP, CD1E, CD1C, and CD1B) might show a potentially good performance in predicting overall survival in patients with LUAD. In summary, we identified the key genes related to the microenvironment, which can further serve as the prognostic biomarkers and therapeutic targets for LUAD.

scholarly journals Identification of Key Prognosis-Associated Genes in the Lung Adenocarcinoma

2020 ◽  
Author(s):  
HongBo Ma ◽  
XiaoLi Wu ◽  
MiaoMiao Tao ◽  
Uthaman Jithin ◽  
GenDou Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Prognostic Biomarkers ◽  
Key Genes ◽  
The Impact

Abstract Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death globally, and lung adenocarcinoma (LUAD) accounts for almost 40% of all lung cancer cases. In recent years, despite better understanding of the pathogenesis of the disease and achievements in the multimodal treatment of tumors, there is an urgent need to identify new diagnostic and prognostic biomarkers In this study, we aim to identify the potential key genes related to the pathogenesis and prognosis of LUAD by using comprehensive bioinformatics analysis. The gene expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, and we calculated the LUAD immune scores and stromal scores by using the ESTIMATE algorithm. Based on these scores, we further quantified the immune and stromal components and obtained the differentially expressed genes (DEGs) in the tumor. Overall survival analysis could better reflect the impact of genes related to immune and stromal cells on the prognosis. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted, while protein-protein interaction (PPI) network was obtained from STRING. Analysis of the correlation revealed that these genes are mainly involved in the immune/inflammatory response. In conclusion, our study showed that 11 prognostic genes (CD33, IRF8, CD80, CD53, IL16, LY86, CD79B, TYROBP, CD1E, CD1C, and CD1B) might show a potentially good performance in predicting overall survival in patients with LUAD. In summary, we identified the key genes related to the microenvironment, which can further serve as the prognostic biomarkers and therapeutic targets for LUAD.

Identify Key Genes by Weighted Gene Co-Expression Network Analysis for Lung Adenocarcinoma

Nano LIFE ◽  
2019 ◽  
Vol 09 (01n02) ◽  
pp. 1940002
Author(s):  
Jichen Xu ◽  
Xianchun Zong ◽  
Qianshu Ren ◽  
Hongyu Wang ◽  
Lijuan Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Oocyte Meiosis ◽  
Key Genes

The aim of this paper is to identify key genes in lung adenocarcinoma (LUAD) through weighted gene co-expression network analysis (WGCNA), and to further understand the molecular mechanism of LUAD. 107 gene expression profiles were downloaded from GSE10072 in the GEO database. We performed rigorous processing of the initial gene expression profile data. Subsequently, we used WGCNA to identify disease-driven modules and enforced functional enrichment analysis. The key genes were defined as the most connected genes in the driver module and were validated using the GSE75037 and TCGA database. GSE10072 removed 41 unpaired lung samples and 4 outliers. By analyzing the 62 samples using WGCNA, we obtained 26 modules and identified the brown and magenta modules as the driving modules for the LUAD. We found that the “Cell cycle”, “Oocyte meiosis” and “Progesterone-mediated oocyte maturation” pathways may be related to the occurrence of LUAD. GSE75037 removed 8 outlier and obtained 2909 differentially expressed genes (DEGs), 26 genes (9 genes in the brown module, 17 genes in the magenta module) overlap with key genes in the driver module. The results of the survival analysis suggest that 19 genes were significantly correlated with the patient’s survival time, including KPNA2, FEN1, RRM2, TOP2A, CENPF, MCM4, BIRC5, MELK, MAD2L1, CCNB1, CCNA2, KIF11, CDKN3, NUSAP1, CEP55, AURKA, NEK2, KIF14 and CDCA8, which may be potential biomarkers or therapeutic targets for LUAD. In this study, we provide a theoretical basis for further understanding the biological mechanism of LUAD through bioinformatics analysis of LUAD.

scholarly journals Identification of key prognosis-associated genes in the lung adenocarcinoma

2020 ◽  
Author(s):  
HongBo Ma ◽  
XiaoLi Wu ◽  
MiaoMiao Tao ◽  
Uthaman Jithin ◽  
GenDou Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Prognostic Biomarkers ◽  
Key Genes ◽  
The Impact

Abstract Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death globally, and lung adenocarcinoma (LUAD) accounts for almost 40% of all lung cancer cases. In recent years, despite better understanding of the pathogenesis of the disease and achievements in the multimodal treatment of tumors, there is an urgent need to identify new diagnostic and prognostic biomarkers In this study, we aim to identify the potential key genes related to the pathogenesis and prognosis of LUAD by using comprehensive bioinformatics analysis. The gene expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, and we calculated the LUAD immune scores and stromal scores by using the ESTIMATE algorithm. Based on these scores, we further quantified the immune and stromal components and obtained the differentially expressed genes (DEGs) in the tumor. Overall survival analysis could better reflect the impact of genes related to immune and stromal cells on the prognosis. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted, while protein-protein interaction (PPI) network was obtained from STRING. Analysis of the correlation revealed that these genes are mainly involved in the immune/inflammatory response. In conclusion, our study showed that 11 prognostic genes (CD33, IRF8, CD80, CD53, IL16, LY86, CD79B, TYROBP, CD1E, CD1C, and CD1B) might show a potentially good performance in predicting overall survival in patients with LUAD. In summary, we identified the key genes related to the microenvironment, which can further serve as the prognostic biomarkers and therapeutic targets for LUAD.

scholarly journals Identification of a novel cancer stemness-associated ceRNA axis in lung adenocarcinoma via stemness indices analysis

2020 ◽  
Author(s):  
Pihua Han ◽  
Haiming Yang ◽  
Xiang Li ◽  
Jie Wu ◽  
Peili Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cancer Stemness ◽  
Bioinformatics Analyses ◽  
Cerna Network ◽  
Gene Coexpression ◽  
Kaplan Meier

To identify a novel cancer stemness-related ceRNA regulatory axis in lung adenocarcinoma (LUAD) via weighted gene coexpression network analysis of a stemness index. The RNA sequencing expression profiles of 513 cancer samples and 60 normal samples were obtained from the TCGA database. Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) were identified with R software. Functional enrichment analysis was conducted using DAVID 6.8. The ceRNA network was constructed via multiple bioinformatics analyses, and the correlations between possible ceRNAs and prognosis were analyzed using Kaplan-Meier plots. Then, WGCNA was applied to distinguish key genes related to the mRNA expression-based stemness index (mRNAsi) in LUAD. After combining the weighted gene coexpression and ceRNA networks, a novel ceRNA regulatory axis was identified, and its biological functions were explored in vitro and vivo. In total, 1,825 DElncRNAs, 291 DEmiRNAs, and 3,742 DEmRNAs were identified. Functional enrichment analysis revealed that the DEmRNAs might be associated with LUAD onset and progression. The ceRNA network was constructed with 14 lncRNAs, 10 miRNAs and 52 mRNAs. Kaplan-Meier analysis identified 2 DEmiRNAs, 5 DElncRNAs and 41 DEmRNAs with remarkable prognostic power. One gene (MFAP4) in the ceRNA network was found to be closely related to mRNAsi by using WGCNA. Functional investigation further confirmed that the C8orf34-as1/miR-671-5p/MFAP4 regulatory axis has important functions in LUAD cell migration and stemness. This study provides a deeper understanding of the lncRNA-miRNA-mRNA ceRNA network and, more importantly, reveals a novel ceRNA regulatory axis, which may provide new insights into novel molecular therapeutic targets for inhibiting LUAD stem characteristics.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

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