scholarly journals Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7619 ◽  
Author(s):  
Chuanfei Li ◽  
Feng Qin ◽  
Hao Hong ◽  
Hui Tang ◽  
Xiaoling Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Expression Profiles ◽  
Core Gene ◽  
Functional Enrichment ◽  
Potential Core ◽  
Potential Biomarker ◽  
Cancer Tissues ◽  
Core Genes

Hepatocellular carcinoma (HCC) is a common yet deadly form of malignant cancer. However, the specific mechanisms involved in HCC diagnosis have not yet fully elucidated. Herein, we screened four publically available Gene Expression Omnibus (GEO) expression profiles (GSE14520, GSE29721, GSE45267 and GSE60502), and used them to identify 409 differentially expressed genes (DEGs), including 142 and 267 up- and down-regulated genes, respectively. The DAVID database was used to look for functionally enriched pathways among DEGs, and the STRING database and Cytoscape platform were used to generate a protein-protein interaction (PPI) network for these DEGs. The cytoHubba plug-in was utilized to detect 185 hub genes, and three key clustering modules were constructed with the MCODE plug-in. Gene functional enrichment analyses of these three key clustering modules were further performed, and nine core genes including BIRC5, DLGAP5, DTL, FEN1, KIAA0101, KIF4A, MCM2, MKI67, and RFC4, were identified in the most critical cluster. Subsequently, the hierarchical clustering and expression of core genes in TCGA liver cancer tissues were analyzed using the UCSC Cancer Genomics Browser, and whether elevated core gene expression was linked to a poor prognosis in HCC patients was assessed using the GEPIA database. The PPI of the nine core genes revealed an interaction between FEN1, MCM2, RFC4, and BIRC5. Furthermore, the expression of FEN1 was positively correlated with that of three other core genes in TCGA liver cancer tissues. FEN1 expression in HCC and other tumor types was assessed with the FIREBROWSE and ONCOMINE databases, and results were verified in HCC samples and hepatoma cells. FEN1 levels were also positively correlated with tumor size, distant metastasis and vascular invasion. In conclusion, we identified nine core genes associated with HCC development, offering novel insight into HCC progression. In particular, the aberrantly elevated FEN1 may represent a potential biomarker for HCC diagnosis and treatment.

scholarly journals LASSO and Bioinformatics Analysis in the Identification of Key Genes for Prognostic Genes of Gynecologic Cancer

2021 ◽  
Vol 11 (11) ◽  
pp. 1177
Author(s):  
Shao-Hua Yu ◽  
Jia-Hua Cai ◽  
De-Lun Chen ◽  
Szu-Han Liao ◽  
Yi-Zhen Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Pathway Analysis ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Functional Enrichment ◽  
Lasso Regression ◽  
Potential Biomarker ◽  
Study Gene Expression

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium–calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.

scholarly journals Glucose-6-Phosphate Dehydrogenase is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

2022 ◽  
Author(s):  
Yang Bu ◽  
Kejun Liu ◽  
Yiming Niu ◽  
Ji Hao ◽  
Lei Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in the metabolic and immunological aspects of tumors. In hepatocellular carcinoma (HCC), the alteration of tumor microenvironment influences recurrence and metastasis. We extracted G6PD-related data from public databases of HCC tissues and used a bioinformatics approach to explore the correlation between G6PD expression and clinicopathological features and prognosis of immune cell infiltration in HCC.Methods: We extract G6PD expression information from TCGA and GEO databases in liver cancer tissues and normal tissues, validated by immunohistochemistry, and the correlation between G6PD expression and clinical features is analyzed, and the clinical significance of G6PD in liver cancer is assessed by Kaplan-Meier, Cox regression and prognostic line graph models. Functional enrichment analysis is performed by protein-protein interaction (PPI) network, GO/KEGG, GSEA and G6PD-associated differentially expressed genes (DEGs). TIMER and ssGSEA packages are used to assess the correlation between expression and the level of immune cell infiltration.Results: Our results show that G6PD expression is significantly upregulated in hepatocellular carcinoma tissues (P < 0.001). G6PD expression is associated with histological grade, pathological stage, T-stage, vascular infiltration and AFP level (P < 0.05); HCC patients in the low G6PD expression group had longer overall survival and better prognosis compared with the high G6PD expression group (P < 0.05). The level of G6PD expression also affects the levels of macrophages, unactivated dendritic cells, B cells, and follicular helper T cells in the tumor microenvironment.Conclusion: High expression of G6PD is a potential biomarker for poor prognosis of hepatocellular carcinoma, and G6PD may be a target for immunotherapy of HCC.

scholarly journals Potential lncRNA Biomarkers for HBV-Related Hepatocellular Carcinoma Diagnosis Revealed by Analysis on Coexpression Network

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Shunqiang Nong ◽  
Xiaohao Chen ◽  
Zechen Wang ◽  
Guidan Xu ◽  
Wujun Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
Functional Annotation ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Coexpression Network ◽  
Support Vector ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

Background. Increasing evidence demonstrated that long noncoding RNA (lncRNA) could affect inflammatory tumor immune microenvironment by modulating gene expression and could be used as a biomarker for HBC-related hepatocellular carcinoma (HCC) but still needs further research. The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC. Methods. HBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software. Result. A total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app. Conclusion. The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.

scholarly journals Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Shasha Su ◽  
Wenjie Kong ◽  
Jing Zhang ◽  
Xinguo Wang ◽  
Hongmei Guo
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Osteoclast Differentiation ◽  
Functional Enrichment ◽  
Functional Network ◽  
Integrated Analysis ◽  
Genome Wide ◽  
Potential Biomarker

Abstract Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

scholarly journals Identifications of Candidate Genes Significantly Associated With Rectal Cancer by Integrated Bioinformatics Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382097327
Author(s):  
Zhili Xu ◽  
Yan Li ◽  
Yiyi Cui ◽  
Yong Guo
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Candidate Genes ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Receptor Interaction ◽  
Cancer Tissue ◽  
Cancer Tissues ◽  
Core Genes

Introduction: Rectal cancer ranks as the eighth in cancer-related morbidity and the tenth in the cancer-related mortality. A few studies have explored several biomarkers for colorectal cancer. However, there is still a great need for us to excavate novel biomarkers with effective and efficient diagnostic and prognostic values to discover the etiology and pathogenesis of rectal cancer separately. Therefore, we aimed to identify more novel candidate genes that were significantly associated with rectal cancer through integrated bioinformatics analysis. Methods: We analyzed the gene expression profiles of GSE15781 and GSE20842 from Gene Expression Omnibus database to identify differentially expressed genes between normal rectal tissue and rectal cancer tissue. Results: We searched for core genes, carried out survival analysis and analyzed the expressions of core genes. We found that 142 genes were significantly upregulated, and 229 genes were significantly downregulated in all 3 independent studies. In KEGG analysis, the upregulated genes were significantly enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway, cell cycle, etc. The downregulated genes were primarily enriched in nitrogen metabolism, mineral absorption and pentose and glucuronate interconversions. Inhibin subunit beta B (INHBB) expressed markedly higher in rectal cancer tissues compared with normal tissues, and claudins (CLDN) 23 expressed significantly lower in rectal cancer tissues. Conclusion: In conclusion, we discovered that INHBB could provide a great significant diagnostic and prognostic values for rectal cancer.

scholarly journals Integrated Bioinformatic Analysis Revealed the Regulation of Angiogenesis by Tumor Cells in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Meisi Huo ◽  
Kangkang Yu ◽  
Yahui Zheng ◽  
Lu Liu ◽  
Hao Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Tumor Cells ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, metastasis accounts for most of the cases. Angiogenesis plays an important role in cancer metastasis, but how tumor cells affect the function of endothelial cells by dictating their miRNA expression remains largely unknown.Differentially expressed miRNAs (DEMs) were identified through dataset downloaded from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R. We then use online tools to obtain potential targets of candidate microRNAs(miRNAs) and functional enrichment analysis，as well as the protein-protein interaction (PPI). Finally, the function of miR-302c-3p was validated through in vitro assay.In the current study, we found that HCC cells altered miRNAs expression profiles of human umbilical vein endothelial cells (HUVECs) and miR-302c-3p was the most downregulated miRNA in HUVECs when they were co-cultured with HCC-LM3 cells. Functional enrichment analysis of the candidate targets revealed that these genes were involved in epigenetic regulation of gene expression, in particular, histone methylation. In addition, PPI network demonstrated distinct roles of genes targeted by miR-302c-3p. Importantly, inhibition of angiogenesis, migration and permeability by the most downregulated miR-302c-3p in HUVECs was confirmed in vitro. These findings brought us novel insight into the regulation of angiogenesis by HCC cells and provided potential targets for the development of therapeutic strategies.

scholarly journals Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Varicose Veins ◽  
Expression Profiles ◽  
Lower Limbs ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Pathologic Features

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

Identification of CCNB2 expression in triple-negative breast cancer based on bioinformatics results

2021 ◽  
Author(s):  
jintao cao ◽  
SHUAI SUN ◽  
RAN LI ◽  
RUI MIN ◽  
XINGYU FAN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Protein Complex ◽  
Triple Negative ◽  
Expression Profiles ◽  
Pathway Enrichment Analysis ◽  
Analysis Tool ◽  
The Core ◽  
Core Genes

Abstract Background The current epidemiology shows that the incidence of breast cancer is increasing year by year and tends to be younger. Triple-negative breast cancer is the most malignant of breast cancer subtypes. The application of bioinformatics in tumor research is becoming more and more extensive. This study provided research ideas and basis for exploring the potential targets of gene therapy for triple-negative breast cancer (TNBC). Methods We analyzed three gene expression profiles (GSE64790、GSE62931、GSE38959) selected from the Gene Expression Omnibus (GEO) database. The GEO2R online analysis tool was used to screen for differentially expressed genes (DEGs) between TNBC and normal tissues. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify the pathways and functional annotation of DEGs. Protein–protein interaction network of these DEGs were visualized by the Metascape gene-list analysis tool so that we could find the protein complex containing the core genes. Subsequently, we investigated the transcriptional data of the core genes in patients with breast cancer from the Oncomine database. Moreover, the online Kaplan–Meier plotter survival analysis tool was used to evaluate the prognostic value of core genes expression in TNBC patients. Finally, immunohistochemistry (IHC) was used to evaluated the expression level and subcellular localization of CCNB2 on TNBC tissues. Results A total of 66 DEGs were identified, including 33 up-regulated genes and 33 down-regulated genes. Among them, a potential protein complex containing five core genes was screened out. The high expression of these core genes was correlated to the poor prognosis of patients suffering breast cancer, especially the overexpression of CCNB2. CCNB2 protein positively expressed in the cytoplasm, and its expression in triple-negative breast cancer tissues was significantly higher than that in adjacent tissues. Conclusions CCNB2 may play a crucial role in the development of TNBC and has the potential as a prognostic biomarker of TNBC.

scholarly journals Circular RNA Hsa_Circ_0091579 Serves as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

2018 ◽  
Vol 51 (1) ◽  
pp. 290-300 ◽  
Author(s):  
Chenxing Zhang ◽  
Chenyue Zhang ◽  
Jiamao Lin ◽  
Haiyong Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Critical Role ◽  
Roc Curves ◽  
Altered Expression ◽  
Qrt Pcr ◽  
Specificity And Sensitivity ◽  
Tumor Tissues ◽  
Potential Biomarker

Background/Aims: An increasing number of studies have suggested that circular RNAs (circRNAs) have vital roles in carcinogenesis and tumor progression. However, the function of circRNAs in hepatocellular carcinoma (HCC) remains poorly characterized. Methods: We investigated the levels of circRNAs in patients with HCC to identify potential diagnostic biomarkers. We examined circRNA expression profiles in liver tumors and paired non-cancerous liver tissues from three HCC patients with cancer thrombus using a circRNA microarray. Bioinformatics analysis was performed to find circRNAs with significantly altered expression levels between tumors and their paired non-tumor tissues. We confirmed our initial findings by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves were also applied to identify a candidate circRNA with the optimal specificity and sensitivity. Finally, X-tile software was adopted to calculate the most efficient cut-off value for hsa_circ_0091579 expression. Results: Microarray analysis identified 20 unique circRNAs that were differentially expressed between tumor and non-tumor tissues (P < 0.05). The expression of these 20 circRNAs was verified by qRT-PCR. The expression of hsa_circ_16245-1 and hsa_circ_0091579 mRNA was consistent with their levels as tested by the microarray. The ROC curves showed that both hsa_circ_16245-1 and hsa_circ_0091579 had favorable specificity and sensitivity. We further confirmed that hsa_circ_0091579 was significantly upregulated in HCC and its high expression was intimately associated with a worse overall survival in patients with HCC. Conclusion: Hsa_circ_0091579 may play a critical role in HCC progression and serve as a potential biomarker for the prognosis of patients with HCC.

Sign in / Sign up

Export Citation Format

Share Document