hub gene
Recently Published Documents


TOTAL DOCUMENTS

193
(FIVE YEARS 175)

H-INDEX

9
(FIVE YEARS 5)

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiali Meng ◽  
Yuanchao Wei ◽  
Qing Deng ◽  
Ling Li ◽  
Xiaolong Li

Abstract Background Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied. Objective To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis. Methods The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein–protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan–Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients. Results TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.


2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Sen-Yuan Hong ◽  
Qi-Dong Xia ◽  
Jin-Zhou Xu ◽  
Chen-Qian Liu ◽  
Jian-Xuan Sun ◽  
...  

Abstract Background Kidney stone disease (KSD) is a multifactorial disease involving both environmental and genetic factors, whose pathogenesis remains unclear. This study aims to explore the hub genes related to stone formation that could serve as potential therapeutic targets. Methods Based on the GSE73680 dataset with 62 samples, differentially expressed genes (DEGs) between Randall’s plaque (RP) tissues and normal tissues were screened and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with KSD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological functions. The protein–protein interaction (PPI) network was constructed to identify hub genes. Meanwhile, CIBERSORT and ssGSEA analysis were used to estimate the infiltration level of the immune cells. The correlations between hub genes and immune infiltration levels were also investigated. Finally, the top hub gene was selected for further GSEA analysis. Results A total of 116 DEGs, including 73 up-regulated and 43 down-regulated genes, were screened in the dataset. The red module was identified as the key module correlated with KSD. 53 genes were obtained for functional enrichment analysis by taking the intersection of DEGs and genes in the red module. GO analysis showed that these genes were mainly involved in extracellular matrix organization (ECM) and extracellular structure organization, and others. KEGG analysis revealed that the pathways of aldosterone-regulated sodium reabsorption, cell adhesion molecules, arachidonic acid (AA) metabolism, and ECM-receptor interaction were enriched. Through PPI network construction, 30 hub genes were identified. CIBERSORT analysis revealed a significantly increased proportion of M0 macrophages, while ssGSEA revealed no significant differences. Among these hub genes, SPP1, LCN2, MMP7, MUC1, SCNN1A, CLU, SLP1, LAMC2, and CYSLTR2 were positively correlated with macrophages infiltration. GSEA analysis found that positive regulation of JNK activity was enriched in RP tissues with high SPP1 expression, while negative regulation of IL-1β production was enriched in the low-SPP1 subgroup. Conclusions There are 30 hub genes associated with KSD, among which SPP1 is the top hub gene with the most extensive links with other hub genes. SPP1 might play a pivotal role in the pathogenesis of KSD, which is expected to become a potential therapeutic target, while its interaction with macrophages in KSD needs further investigation.


2022 ◽  
Vol 12 ◽  
Author(s):  
Jun Ma ◽  
Tianliu Zhang ◽  
Wenxiang Wang ◽  
Yan Chen ◽  
Wentao Cai ◽  
...  

Gayal and yak are well adapted to the local high-altitude environments, yet the transcriptional regulation difference of the plateau environment among them remains obscure. Herein, cross-tissue and cross-species comparative transcriptome analysis were performed for the six hypoxia-sensitive tissues from gayal, yak, and cattle. Gene expression profiles for all single-copy orthologous genes showed tissue-specific expression patterns. By differential expression analysis, we identified 3020 and 1995 differentially expressed genes (DEGs) in at least one tissue of gayal vs. cattle and yak vs. cattle, respectively. Notably, we found that the adaptability of the gayal to the alpine canyon environment is highly similar to the yak living in the Qinghai-Tibet Plateau, such as promoting red blood cell development, angiogenesis, reducing blood coagulation, immune system activation, and energy metabolism shifts from fatty acid β-oxidation to glycolysis. By further analyzing the common and unique DEGs in the six tissues, we also found that numerous expression regulatory genes related to these functions are unique in the gayal and yak, which may play important roles in adapting to the corresponding high-altitude environment. Combined with WGCNA analysis, we found UQCRC1, COX5A are the shared differentially expression hub genes related to the energy supply of myocardial contraction in the heart-related modules of gayal and yak, and CAPS is a shared differentially hub gene among the hub genes of the lung-related module, which is related to pulmonary artery smooth muscle contraction. Additionally, EDN3 is the unique differentially expression hub gene related to the tracheal epithelium and pulmonary vasoconstriction in the lung of gayal. CHRM2 is a unique differentially expression hub gene that was identified in the heart of yak, which has an important role in the autonomous regulation of the heart. These results provide a basis for further understanding the complex transcriptome expression pattern and the regulatory mechanism of high-altitude domestication of gayal and yak.


2022 ◽  
Vol 11 ◽  
Author(s):  
Hao Wen ◽  
Qin-Hao Guo ◽  
Xiao-Lan Zhou ◽  
Xiao-Hua Wu ◽  
Jin Li

BackgroundCervical cancer is responsible for 10–15% of cancer-related deaths in women worldwide. In China, it is the most common cancer in the female genital tract. However, the genomic profiles of Chinese cervical cancer patients remain unclear.Materials and MethodsA total of 129 cervical cancer patients were enrolled in this study (113 squamous, 12 adenocarcinoma, 2 adenosquamous, and 2 neuroendocrine carcinoma). To classify the clinical features and molecular characteristics of cervical cancer, the genomic alterations of 618 selected genes were analyzed in the samples of these patients, utilizing target next-generation sequencing (NGS) technology. Furthermore, the findings from the Chinese cohort were then compared with the data of Western patients downloaded from The Cancer Genome Atlas (TCGA) database, in terms of gene expression files, mutation data, and clinical information.ResultsAll studied patients had valid somatic gene alterations, and the most frequently altered genes were PIK3C, TP53, FBXW7, ARID1A, ERBB2, and PTEN. Comparison of genomic profiling showed significantly different prevalence of genes, including TP53, KMT2C, and RET, between the Chinese and the TCGA cohorts. Moreover, 57 patients (44.19%) with 83 actionable alterations were identified in our cohort, especially in PI3K and DNA damage repair (DDR) pathways. After an in-depth analysis of cervical cancer data from the TCGA cohort, DDR alteration was found to be associated with extremely higher tumor mutation burden (TMB) (median mutation count: 149.5 vs 66, p <0.0001), and advanced stages (p <0.05). Additionally, DDR alteration, regardless of its function, was positively correlated with hypoxia feature and score. Moreover, patients with a high hypoxia score were positively correlated with a high abundance of mast cell resting, but lower abundance of CD8+ T cells and activated mast cell. Finally, CDHR5 was identified as the hub gene to be involved in the DDR–hypoxia network, which was negatively correlated with both the DDR alteration and hypoxia score.ConclusionsOverall, a unique genomic profiling of Chinese patients with cervical cancer was uncovered. Besides, the prevalent actionable variants, especially in PI3K and DDR pathways, would help promote the clinical management. Moreover, DDR alteration exerted the significant influence on the tumor microenvironment in cervical cancer, which could guide the clinical decisions for the treatment. CDHR5 was the first identified hub gene to be negatively correlated with DDR or hypoxia in cervical cancer, which had potential effects on the treatment of immune checkpoint inhibitors (ICIs).


2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Feng Jiang ◽  
Yifang Hu ◽  
Xiaoqin Liu ◽  
Ming Wang ◽  
Chuyan Wu

Background. Recent research has established the existence of epigenetic modulation of the immune response. The possible involvement of RNA-n6-methyladenosine (m6A) alteration in tumor microenvironment (TME) cell invasion, on the other hand, is unknown. Methods. Based on 23 m6A regulators, we examined the alteration patterns of m6A in 629 LUAD tissues and comprehensively connected these modification patterns with TME cell invasion characteristics. The m6A score was calculated, and the m6A modification pattern of a single tumor was quantified using principal component analysis. Then, we further verified the expression of m6A related enzymes and the role hub gene (NOL10) closely related to survival in lung cancer cell lines. Results. Three separate m6A alteration modes have been discovered. TME cell invasion characteristics in the three modes were very similar to the three immunological phenotypes of tumors: immunological rejection, immunological inflammation, and immunological desert. We show that assessing the m6A modification pattern in a single tumor may help predict tumor inflammatory stage, subtype, TME interstitial activity, and prognosis. TME phenotypic inflammation is indicated by a high m6A score, which is characterized by elevated mutation load and immunological activation. The low m6A subtype showed matrix activation and ineffective immune infiltration, indicating that the TME phenotype of noninflammation and immunological rejection had a poor survival probability. Increased neoantigen burden was also linked to a high m6A score. Patients with a higher m6A score saw substantial therapeutic and clinical improvements. And reducing hub gene NOL10 expression substantially inhibited lung cancer cell growth and migration. Conclusions. This research shows that m6A alteration is critical in the creation of TME variety and complexity. The analysis of a single tumor’s m6A alteration pattern will aid in improving our knowledge of TME invasion features and guiding more effective immunotherapy tactics.


2022 ◽  
Vol 12 ◽  
Author(s):  
Ronghua Yang ◽  
Zhengguang Wang ◽  
Jiehua Li ◽  
Xiaobing Pi ◽  
Xiaoxiang Wang ◽  
...  

Background: Burn injury is a life-threatening disease that does not have ideal biomarkers. Therefore, this study first applied weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening methods to identify pivotal genes and diagnostic biomarkers associated with the skin burn process.Methods: After obtaining transcriptomic datasets of burn patient skin and normal skin from Gene Expression Omnibus (GEO) and performing differential analysis and functional enrichment, WGCNA was used to identify hub gene modules associated with burn skin processes in the burn patient peripheral blood sample dataset and determine the correlation between modules and clinical features. Enrichment analysis was performed to identify the functions and pathways of key module genes. Differential analysis, WGCNA, protein-protein interaction analysis, and enrichment analysis were utilized to screen for hub genes. Hub genes were validated in two other GEO datasets, tested by immunohistochemistry for hub gene expression in burn patients, and receiver operating characteristic curve analysis was performed. Finally, we constructed the specific drug activity, transcription factors, and microRNA regulatory network of the five hub genes.Results: A total of 1,373 DEGs in GSE8056 were obtained, and the top 5 upregulated genes were S100A12, CXCL8, CXCL5, MMP3, and MMP1, whereas the top 5 downregulated genes were SCGB1D2, SCGB2A2, DCD, TSPAN8, and KRT25. DEGs were significantly enriched in the immunity, epidermal development, and skin development processes. In WGCNA, the yellow module was identified as the most closely associated module with tissue damage during the burn process, and the five hub genes (ANXA3, MCEMP1, MMP9, S100A12, and TCN1) were identified as the key genes for burn injury status, which consistently showed high expression in burn patient blood samples in the GSE37069 and GSE13902 datasets. Furthermore, we verified using immunohistochemistry that these five novel hub genes were also significantly elevated in burn patient skin. In addition, MCEMP1, MMP9, and S100A12 showed perfect diagnostic performance in the receiver operating characteristic analysis.Conclusion: In conclusion, we analyzed the changes in genetic processes in the skin during burns and used them to identify five potential novel diagnostic markers in blood samples from burn patients, which are important for burn patient diagnosis. In particular, MCEMP1, MMP9, and S100A12 are three key blood biomarkers that can be used to identify skin damage in burn patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Huan Mei ◽  
Bowen Qi ◽  
Zegang Han ◽  
Ting Zhao ◽  
Menglan Guo ◽  
...  

As two cultivated widely allotetraploid cotton species, although Gossypium hirsutum and Gossypium barbadense evolved from the same ancestor, they differ in fiber quality; the molecular mechanism of that difference should be deeply studied. Here, we performed RNA-seq of fiber samples from four G. hirsutum and three G. barbadense cultivars to compare their gene expression patterns on multiple dimensions. We found that 15.90–37.96% of differentially expressed genes showed biased expression toward the A or D subgenome. In particular, interspecific biased expression was exhibited by a total of 330 and 486 gene pairs at 10 days post-anthesis (DPA) and 20 DPA, respectively. Moreover, 6791 genes demonstrated temporal differences in expression, including 346 genes predominantly expressed at 10 DPA in G. hirsutum (TM-1) but postponed to 20 DPA in G. barbadense (Hai7124), and 367 genes predominantly expressed at 20 DPA in TM-1 but postponed to 25 DPA in Hai7124. These postponed genes mainly participated in carbohydrate metabolism, lipid metabolism, plant hormone signal transduction, and starch and sucrose metabolism. In addition, most of the co-expression network and hub genes involved in fiber development showed asymmetric expression between TM-1 and Hai7124, like three hub genes detected at 10 DPA in TM-1 but not until 25 DPA in Hai7124. Our study provides new insights into interspecific expression bias and postponed expression of genes associated with fiber quality, which are mainly tied to asymmetric hub gene network. This work will facilitate further research aimed at understanding the mechanisms underlying cotton fiber improvement.


2021 ◽  
Author(s):  
Zhi-Hui Li ◽  
Guang-Tian Wang ◽  
Chun-Ling Chi ◽  
Yu-Nan Zhou ◽  
Dan Liu ◽  
...  

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD remains elusive, however PD appears to be caused by a complex interaction between environmental and genetic factors affecting various biological processes. The purpose of the present study is to identify hub genes and potential molecular mechanisms in peripheral blood mononuclear cells (PBMCs) of PD patients to aid early diagnosis and start treatment promptly. Two gene expression profiles (GSE22491 and GSE100054) were obtained from the Gene Expression Omnibus (GEO) database, in which 20 PBMC samples from PD patients and 17 controls were included, and the genes were analyzed with GEO2R. 1382 and 512 differentially expressed genes (DEGs) were identified in GSE22491 and GSE100054, respectively. Additionally, a total of 80 significant DEGs were found to co-exist in the two microarray datasets via Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, which showed that the DEGs were mainly enriched in platelet degranulation, blood coagulation, nitric oxide mediated signal transduction, positive regulation of GTPase activity and cellular response to lipopolysaccharide. PPI network, microRNA (miRNA) - hub gene network, and transcription factor (TF)- hub gene network were constructed. In summary, the present study provides data of potential diagnostic biomarkers and therapeutic targets for PD. SRC may be a potential target for the treatment of PD. Additionally, three TFs (HNF4A, CDX2 and FUS), three miRNAs (hsa-miR-16-5p, hsa-miR-103a-3p and hsa-miR-107), may be involved in PD.


2021 ◽  
Author(s):  
Basavaraj Mallikarjunayya Vastrad ◽  
Chanabasayya Mallikarjunayya Vastrad

Non alcoholic fatty liver disease (NAFLD) is the most common metabolic disease in humans, affecting the majority of individuals. In the current investigation, we aim to identify potential key genes linked with NAFLD through bioinformatics analyses of next generation sequencing (NGS) dataset. NGS dataset of GSE135251 from the Gene Expression Omnibus (GEO) database were retrieved. Differentially expressed genes (DEGs) were obtained by DESeq2 package. g:Profiler database was further used to identify the potential gene ontology (GO) and REACTOME pathways. Protein-protein interaction (PPI) network was constructed using the Hippie interactome database. miRNet and NetworkAnalyst databases were used to establish a miRNA-hub gene regulatory network and TF-hub gene regulatory network for the hub genes. Hub genes were verified based on receiver operating characteristic curve (ROC) analysis. Totally, 951 DEGs were identified including 476 up regulated genes and 475 down regulated genes screened in NAFLD and normal control. GO showed that DEGs were significantly enhanced for signaling and regulation of biological quality. REACTOME pathway analysis revealed that DEGs were enriched in signaling by interleukins and extracellular matrix organization. ESR2, JUN, PTN, PTGER3, CEBPB, IKBKG, HSPA8, SFN, CDKN1A and E2F1 were indicated as hub genes from PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Furthermore, ROC analysis revealed that ESR2, JUN, PTN, PTGER3, CEBPB, IKBKG, HSPA8, SFN, CDKN1A and E2F1 might serve as diagnostic biomarkers in NAFLD. The current investigation provided insights into the molecular mechanism of NAFLD that might be useful in further investigations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Ning ◽  
Mengzhi Li ◽  
Guangfei Wei ◽  
Yuxin Zhou ◽  
Guozhuang Zhang ◽  
...  

Panax notoginseng (Panax notoginseng (Burk.) F.H. Chen), a plant of high medicinal value, is severely affected by root rot during cultivation. Here, we generated a reference genome of P. notoginseng, with a contig N50 size of 241.268 kb, and identified 66 disease-resistance genes (R-genes) as candidate genes for breeding disease-resistant varieties. We then investigated the molecular mechanism underlying the responses of resistant and susceptible P. notoginseng genotypes to Fusarium oxysporum infection at six time points by RNA-seq. Functional analysis of the genes differentially expressed between the two genotypes indicated that genes involved in the defense response biological process like hormone transduction and plant-pathogen interaction are continuously and highly expressed in resistant genotype during infection. Moreover, salicylic acid and jasmonic acid levels gradually increased during infection in the resistant genotype. Coexpression analysis showed that PnWRKY22 acts as a hub gene in the defense response of the resistant genotype. Finally, transiently overexpressing PnWRKY22 increased salicylic acid levels in P. notoginseng leaves. Our findings provide a theoretical basis for studying root rot resistance in P. notoginseng.


Sign in / Sign up

Export Citation Format

Share Document