scholarly journals Identifying and Validating Potential Biomarkers of Early Stage Lung Adenocarcinoma Diagnosis and Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingji Chen ◽  
Longyu Jin ◽  
Zhibin Jiang ◽  
Suo Liu ◽  
Wei Feng
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Ppi Network ◽  
Hub Genes ◽  
Promote Cell Proliferation ◽  
Protein Protein Interaction ◽  
Elevated Expression ◽  
Potential Biomarkers

BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. At present, most patients with LUAD are diagnosed at an advanced stage, and the prognosis of advanced LUAD is poor. Hence, we aimed to identify novel biomarkers for the diagnosis and treatment of early stage LUAD and to explore their predictive value.MethodsThe microarray datasets GSE63459, GSE27262, and GSE33532 were searched, and the differentially expressed genes (DEGs) were obtained using GEO2R. The DEGs were subjected to gene ontology (GO) and pathway enrichment analyses using METASCAPE. A protein–protein interaction (PPI) network was plotted with STRING and visualized by Cytoscape. Module analysis of the PPI network was performed using MCODE. Overall survival (OS) analysis and analysis of the mRNA expression levels of genes identified by MCODE were performed with UALCAN. Western blot analysis of hub genes in LUAD patients, MTS assays, and clonogenic assays were performed to test the effects of the hub genes on cell proliferation in vitro.ResultsA total of 341 DEGs were obtained, which were mainly enriched in terms related to blood vessel development, growth factor binding, and extracellular matrix organization. A PPI network consisting of 300 nodes and 1140 edges was constructed, and a significant module including 15 genes was identified. Elevated expression of ASPM, CCNB2, CDCA5, PRC1, KIAA0101, and UBE2T was associated with poor OS in LUAD patients. In the protein level, the hub gene was overexpressed in LUAD patients. In vitro experiments showed that knockdown of the hub genes in the LUAD cell lines could promote cell proliferation.ConclusionsDEGs are potential biomarkers for early stage lung adenocarcinoma and could have utility for the diagnosis and predicting treatment efficacy.

scholarly journals Bioinformatics Approach to Identify Common Gene Signatures of Patients With Coronavirus 2019 and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Xiao Liang ◽  
Yali Chen ◽  
Yuchao Fan
Keyword(s):  
Lung Adenocarcinoma ◽  
Severe Disease ◽  
Enrichment Analysis ◽  
Immune Checkpoints ◽  
Specific Gene ◽  
Ppi Network ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Tf Gene

Abstract Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman’s correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), cellular component (CC) as well as to pathways, specific organs, cells and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.

scholarly journals Linc00342 serves as a diagnostic and prognostic biomarker in Kidney Renal Clear Cell Carcinoma:A Comprehensive Study Based on Data mining, Clinical Analysis, and in vitro Validation

2020 ◽  
Author(s):  
Di Guan ◽  
Yuexin Liu ◽  
Hao Ping
Keyword(s):  
Cell Proliferation ◽  
Prognostic Value ◽  
Clear Cell ◽  
Early Stage ◽  
Flow Cytometric Analysis ◽  
Clinical Analysis ◽  
Biological Functions ◽  
Promote Cell Proliferation ◽  
Diagnostic And Prognostic Value

Abstract Background: Kidney renal clear cell carcinoma (KIRC), as the most common type of renal cancer, has a high mortality and recurrence rate due to the fact that many patients are in advanced stage at the time of consultation. Finding a biological marker for early-stage KIRC has become a top priority. Recently, accumulating studies have shown that lncRNA can serve as a target for diagnosis and prognosis of malignancy. However, the involvement and mechanism of linc00342 has never been researched in KIRC. The aim of this study was to investigate the diagnostic and prognostic value of linc00342 in KIRC, and to explore the effects of linc00342 on the biological functions of KIRC cells.Methods: We downloaded the linc00342 expression data and clinical information of KIRC from the TCGA database and constructed a prognostic prediction model. In vitro, the effect of knocking down linc00342 on KIRC cell proliferation, apoptosis, metastasis, and invasion was measured by colony-formation assay, flow cytometric analysis, wound-healing assay and Transwell assay, respectively.Results: Our nomogram predictive model suggested linc00342 can serve as an independent prognostic factor for KIRC. GO functional analysis and KEGG pathway analysis showed linc00342 was involved in various biological functions of KIRC, and experiments in vitro verified this. In vitro, linc00342 was overexpressed in KIRC cells as shown by RT-qPCR. Moreover, we found that linc00342 can inhibit cell apoptosis and promote cell proliferation, invasion, and migration.Conclusions: Our study is the first to examine the diagnostic and prognostic value of linc00342 in KIRC and provides new ideas for the treatment of KIRC.

scholarly journals Identification of Pulpitis-Related Potential Biomarkers Using Bioinformatics Approach

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bingchang Xin ◽  
Yuxiang Lin ◽  
He Tian ◽  
Jia Song ◽  
Liwei Zhang ◽  
...  
Keyword(s):  
Inflammatory Reaction ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Hub Genes ◽  
Pulp Tissue ◽  
Network Nodes ◽  
Protein Protein Interaction ◽  
Pathogen Elimination ◽  
Potential Biomarkers ◽  
Geo Database

Inflammatory reaction of pulp tissue plays a role in the pathogen elimination and tissue repair. The evaluation of severity of pulpitis can serve an instructive function in therapeutic scheme. However, there are many limitations in the traditional evaluation methods for the severity of pulpitis. Based on the Gene Expression Omnibus (GEO) database, our study discovered 843 differentially expressed genes (DEGs) related to pulpitis. Afterwards, we constructed a protein-protein interaction (PPI) network of DEGs and used MCODE plugin to determine the key functional subset. Meanwhile, genes in the key functional subset were subjected to GO and KEGG enrichment analyses. The result showed that genes were mainly enriched in inflammatory reaction-related functions. Next, we screened out intersections of PPI network nodes and pulpitis-related genes. Then, 20 genes were obtained as seed genes. In the PPI network, 50 genes that had the highest correlation with seed genes were screened out using random walk with restart (RWR). Furthermore, 4 pulpitis-related hub genes were obtained from the intersection of the top 50 genes and genes in the key functional subset. Finally, GeneMANIA was utilized to predict genes coexpressed with hub genes, and expression levels of the 4 hub genes in normal and pulpitis groups were analyzed based on GEO data. The result demonstrated that the 4 hub genes were mainly coexpressed with chemokine-related genes and were remarkably upregulated in the pulpitis group. In short, we eventually determined 4 potential biomarkers of pulpitis.

scholarly journals Identification of Potential Biomarkers in PBMC of Systemic Lupus Erythematosus: Results from Bioinformatic Analysis

2021 ◽  
Author(s):  
Yan Sun ◽  
Chen-chen Wang ◽  
Fu-quan Wang ◽  
Rui Chen ◽  
Chun-lin Yao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bioinformatic Analysis ◽  
Organ Damage ◽  
Specific Gene ◽  
Ppi Network ◽  
Systemic Lupus ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Potential Biomarkers

Abstract BackgroundThe discovery of biomarkers has become an attractive field in studying autoimmune diseases. For example, in the study of systemic lupus erythematosus (SLE), various biomarkers such as genes and miRNAs have been identified for the diagnosis of SLE and its organ involvement. ResultsThe expression data of gene microarray GSE50772 was downloaded from the GEO, and 257 differentially expressed genes (DEGs) were obtained by using limma plug-in for R software. The tissue-specific gene expression analyses were performed in BioGPS database. Then, a protein-protein interaction (PPI) network was constructed with STRING and visualized in Cytoscape. Whereafter, top twenty hub genes derived from the PPI network, could basically differentiate the SLE samples from the non-SLE samples, were ascertained through CytoHubba. What is noticeable is that the five novel hub genes ( ORM1, SLPI, OLFM4, TCN1 and CRISP3) and a related miRNA (hsa-let-7e-5p) may be considered as candidate biomarkers of SLE. ConclusionsFive genes (ORM1, SLPI, OLFM4, TCN1 and CRISP3) and a miRNA(hsa-let-7e-5p) in this discovery-driven study may become potential biomarkers for diagnosing SLE and assessing its organ damage, and they also will provide valuable information on the pathogenesis of SLE.

scholarly journals Identification of Key Genes and Pathways in Gefitinib-Resistant Lung Adenocarcinoma using Bioinformatics Analysis

2021 ◽  
Vol 17 ◽  
pp. 117693432110237
Author(s):  
Kailin Mao ◽  
Fang Lin ◽  
Yingai Zhang ◽  
Hailong Zhou
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Underlying Mechanisms ◽  
Gefitinib Resistance

Gefitinib resistance is a serious threat in the treatment of patients with non-small cell lung cancer (NSCLC). Elucidating the underlying mechanisms and developing effective therapies to overcome gefitinib resistance is urgently needed. The differentially expressed genes (DEGs) were screened from the gene expression profile GSE122005 between gefitinib-sensitive and resistant samples. GO and KEGG analyses were performed with DAVID. The protein-protein interaction (PPI) network was established to visualize DEGs and screen hub genes. The functional roles of CCL20 in lung adenocarcinoma (LUAD) were examined using gene set enrichment analysis (GSEA). Functional analysis revealed that the DEGs were mainly concentrated in inflammatory, cell chemotaxis, and PI3K signal regulation. Ten hub genes were identified based on the PPI network. The survival analysis of the hub genes showed that CCL20 had a significant effect on the prognosis of LUAD patients. GSEA analysis showed that CCL20 high expression group was mainly enriched in cytokine-related signaling pathways. In conclusion, our analysis suggests that changes in inflammation and cytokine-related signaling pathways are closely related to gefitinib resistance in patients with lung cancer. The CCL20 gene may promote the formation of gefitinib resistance, which may serve as a new biomarker for predicting gefitinib resistance in patients with lung cancer.

scholarly journals Integrated bioinformatic analysis of miR-654-5p target genes and experimental validation of functional analyses

2020 ◽  
Author(s):  
Chuanyang Liu ◽  
Lu Min ◽  
Jingyu Kuang ◽  
Chu-shu Zhu ◽  
Jia-xin Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
In Silico ◽  
Experimental Validation ◽  
Target Genes ◽  
Main Function ◽  
Hub Genes ◽  
Pan Cancer

AbstractBackgroundLung cancer is one of the most malignant types of cancer worldwide. Recently, the pivotal role of miRNAs in carcinogenesis and tumor metastasis have been reported for their direct regulation of specific target genes. However, the precise roles of miR-654-5p in lung adenocarcinoma have been poorly investigated. In this study, we designed a series of closed-loop integrated bioinformatic analyses and in vitro experimental validation to explore the main function and regulation pattern of miR-654-5p, and elucidate its roles in lung adenocarcinoma metastasis and prognosis both in silico and in vitro.MethodData from The Cancer Genome Atlas (TCGA) were used to analyze the pan-cancer prognostic value of miR-654-5p. miRanda, TargetScan, RNA22 and miRWalks were utilized to screen the targets of miR-654-5p. Metascape and miRWalks were used to perform gene ontology analyses and multiple enrichment analyses. STRING database and Cytoscape were used to construct protein-protein network and identify hub genes. GEPIA 2.0 were used to perform pan-cancer expression and survival analyses of hub genes. The regulation between miRNAs and predicted genes were verified by qPCR, western blotting and dual-luciferase system. In addition, EMT hallmarks detection, cell proliferation assay and wound healing assay were used to demonstrate the predicted functions of miR-654-5p experimentally.ResultsWe identified 275 potential targets of miR-654-5p and validated the direct regulatory effects of miR-654-5p on RNF8 in vitro as a proof of concept. Furthermore, we revealed the pivotal functions and disease association of miR-654-5p and experimentally validated the tumor suppressor roles of miR-645-5p that inhibited lung cancer cell epithelial-mesenchymal transition process, cell proliferation, and migration capacity. Among these 275 targets, 11 highly interconnected hub genes in lung adenocarcinoma were selected and studied through pan-cancer expression and pan-cancer survival analysis, in order to assess these targets’ clinical value.Conclusionsour research not only identified 275 hub target genes of miR-654-5p in silico and performed experimental validation but also revealed the tumor-suppressive roles of miR-654-5p in lung adenocarcinoma metastasis in vitro for the first time.

scholarly journals Identification of Hub Genes Associated with Lung Adenocarcinoma Based on Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shuaiqun Wang ◽  
Xiaoling Xu ◽  
Wei Kong
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Limma Package ◽  
Differential Genes

Lung adenocarcinoma (LUAD) is one of the malignant lung tumors. However, its pathology has not been fully understood. The purpose of this study is to identify the hub genes associated with LUAD by bioinformatics methods. Three gene expression datasets including GSE116959, GSE74706, and GSE85841 downloaded from the Gene Expression Omnibus (GEO) database were used in this study. The differentially expressed genes (DEGs) related to LUAD were screened by using the limma package. Gene Ontology (GO) and KEGG analysis of DEGs were carried out through the DAVID website. The protein-protein interaction (PPI) of differentially expressed genes was drawn by the STRING website, and the results were imported into Cytoscape for visualization. Then, the PPI network was analyzed by using MCODE, and the modules with a score greater than 5 were found by using cytoHubba. Finally, the GEPIA database and UALCAN database were used to verify and analyze the survival of hub genes. We identified 67 upregulated genes and 277 downregulated genes from three LUAD datasets. The results of GO analysis showed that the downregulated genes were significantly enriched in matrix adhesion and angiogenesis and upregulated differential genes were significantly enriched in cell adhesion and vascular development. KEGG pathway analysis showed that the differential genes of LUAD were significantly enriched in viral carcinogenesis and adhesion spots. The PPI network of differentially expressed genes consists of 269 nodes and 625 interactions. In addition, three modules with scores greater than 5 and seven hub genes, namely, MCM4, BIRC5, CDC20, CDC25C, FOXM1, GTSE1, and RFC4, playing an important role in the PPI network were screened out. In this study, we obtained the hub genes and pathways related to LUAD, revealing the molecular mechanism and pathogenesis of LUAD, which is helpful for the early detection of LUAD and provides a new idea for the treatment of LUAD.

scholarly journals Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Candidate Genes ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

scholarly journals Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Weishuang Xue ◽  
Jinwei Li ◽  
Kailei Fu ◽  
Weiyu Teng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Bioinformatics Analysis ◽  
Gene Expression Omnibus ◽  
Venn Diagram ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Ppi Networks

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.

Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and Lipogenesis of the 3T3-L1 Preadipocytes

2015 ◽  
Vol 43 (05) ◽  
pp. 915-925 ◽  
Author(s):  
Shou-Lun Lee ◽  
Hsien-Kuang Lee ◽  
Ting-Yu Chin ◽  
Ssu-Chieh Tu ◽  
Ming-Hsun Kuo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sweet Potato ◽  
Early Stage ◽  
Water Extract ◽  
Potato Leaf ◽  
Purple Sweet Potato ◽  
Pre Treatment ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program.

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