Common Nevus and Skin Cutaneous Melanoma: Prognostic Genes Identified by Gene Co-Expression Network Analysis

Skin cutaneous melanoma (SCM) is a common malignant tumor of the skin and its pathogenesis still needs to be studied. In this work, we constructed a co-expression network and screened for hub genes by weighted gene co-expression network analysis (WGCNA) using the GSE98394 dataset. The relationship between the mRNA expression of hub genes and the prognosis of patients with melanoma was validated by Gene Expression Profiling Interactive Analysis (GEPIA) database. Furthermore, immunohistochemistry in the Human Protein Atlas was used to validate hub genes and grayscale analysis was performed using ImageJ software. It was found that the yellow module was most significantly associated with the difference between common nevus and SCM, and 13 genes whose expression correlation >0.9 were candidate hub genes. The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of SCM. STK26 (P = 0.0024) and KCNT2 (P < 0.0001) were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future.

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Ultrasonographic findings of re-epithelialized skin after partial-thickness burns

Burns & Trauma ◽

10.1186/s41038-018-0122-3 ◽

2018 ◽

Vol 6 ◽

Author(s):

Jong Dae Kim ◽

Suk Joon Oh ◽

Sun Gyu Kim ◽

Song Vogue Ahn ◽

Yu Jin Jang ◽

...

Keyword(s):

Medical Records ◽

Normal Skin ◽

Healing Time ◽

Ultrasound Images ◽

Strongly Correlated ◽

Varying Thickness ◽

Partial Thickness ◽

The Difference ◽

Partial Thickness Burns ◽

The Relationship

Abstract Background This study aimed to investigate the difference between ultrasonographic findings of normal skin and those of re-epithelialized skin after partial-thickness burns and to evaluate the relationship between these findings and clinical outcomes. Methods This study retrospectively analysed the ultrasound images of re-epithelialized skin after partial-thickness burns and contralateral normal skin from January 2016 to December 2016. A total of 155 lesions from 148 patients were analysed with ultrasound images, and healing time was documented. The scar status of each lesion was evaluated through medical records and photographs. We analysed the difference in ultrasonographic findings between normal skin and re-epithelialized skin after partial-thickness burns and statistically analysed the relationship between healing time, scar status and ultrasonographic findings. Results The re-epithelialized skin after partial-thickness burns was significantly thicker than the contralateral normal skin, and the echogenicity was significantly lower. The ultrasound images of the re-epithelialized skin after partial-thickness burns showed the characteristic findings of low-echogenic bands (LEB), and the proportion of LEB thickness is strongly correlated with healing time. In the multivariate analysis of scar status, only the proportion of LEB thickness was statistically significant. Conclusion In this study, we found that there were ultrasonographic differences between re-epithelialized skin after partial-thickness burns and normal skin and that an LEB of varying thickness was formed after re-epithelialization. The thickness of the LEB in re-epithelialized skin after partial-thickness burns increased with healing time and was related to scar status.

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Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma

BioMed Research International ◽

10.1155/2020/4145164 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Ya Guo ◽

Zhong Wei Wang ◽

Wang Hui Su ◽

Jing Chen ◽

Ya Li Wang

Keyword(s):

Poor Prognosis ◽

Immune Cell ◽

Genetic Alterations ◽

Prognostic Biomarkers ◽

Venn Diagram ◽

Hub Genes ◽

Immune Infiltration ◽

Interactive Analysis ◽

Human Protein Atlas ◽

Stomach Adenocarcinoma

Background. Stomach adenocarcinoma (STAD) is a common malignancy worldwide with poor prognosis. Therefore, it is important to identify a valuable prognostic biomarker for STAD. The aim of present study was to identify novel prognostic biomarkers for STAD and evaluate the potential role of hub genes in STAD. Methods. Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer RNA-Seq Nexus were performed to identify differentially expressed genes (DEGs). Subsequently, hub genes were selected by a Venn diagram, and the expression of key genes was confirmed by UALCAN database. Furthermore, survival analysis of these hub genes was performed using Oncolnc and Human Protein Atlas (HPA) database. Gene alteration status of hub genes was assessed by cBioPortal. Finally, we investigated the association between hub genes and immune cell infiltration in STAD through the Tumor Immune Estimation Resource (TIMER) and GEPIA database. Results. Three common hub genes were obtained, including 2 downregulated DEGs (ABCA8 and FABP4) and one upregulated DEG (SLC52A3). Furthermore, increased expression of ABCA8 and FABP4 and decreased expression of SLC52A3 were correlated with poor prognosis. Meanwhile, three hub genes showed genetic alterations in various datasets of STAD. Finally, our results showed that ABCA8 and FABP4 displayed a positive correlation with immune infiltration, especially in M2 macrophages. Conclusions. The results of this study suggest that ABCA8 and FABP4 may be used as prognostic biomarkers and correlated with immune infiltration in STAD.

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Identification of immune-related biomarkers associated with tumorigenesis and prognosis in cutaneous melanoma patients

10.21203/rs.2.23305/v3 ◽

2020 ◽

Author(s):

Biao Huang ◽

Wei Han ◽

Zu-Feng Sheng ◽

Guo-Liang Shen

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cd8 T Cells ◽

Cutaneous Melanoma ◽

Normal Skin ◽

Extensive Study ◽

Differentially Expressed ◽

Hub Genes ◽

Bioinformatics Analyses ◽

Normal Tissues

Abstract Background：Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. Methods：Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. Results: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B-cell, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8+T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. Conclusion: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy.

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ERBB1/2/3 Expression, Prognosis, and Immune Infiltration in Cutaneous Melanoma

Frontiers in Genetics ◽

10.3389/fgene.2021.602160 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shougang Liu ◽

Rong Geng ◽

Eryi Lin ◽

Peizhen Zhao ◽

Yongfeng Chen

Keyword(s):

T Cells ◽

Cutaneous Melanoma ◽

Normal Skin ◽

Disease Free Survival ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Erbb Family ◽

Immune Infiltration ◽

Melanoma Patients ◽

The Relationship

BackgroundThe four ERBB tyrosine kinase family members [ERBB1 (epidermal growth factor receptor, EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4)] (ERBB receptor family) have been shown, according to previous studies, to be related to the cutaneous melanoma. ERBB3 is the only member of the ERBBs that lacks tyrosine kinase activity and thus needs to dimer with other tyrosine kinases receptors to trigger the signaling pathway, while ERBB3 may dimer with all members of the ERBB family. Melanoma progression depends on activation of ERBB signaling, especially the ERBB3/ERBB2 cascade. There are lymphocytes and T cell infiltrates in melanoma. Numerous pieces of evidences indicate that local immune status plays an important role in the formation of anti-tumor immune responses. However, the relationship between the ERBBs and prognosis and immune infiltration in cutaneous melanoma is not completely clear.MethodsThe expression of the ERBBs was analyzed through the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), respectively. Immunohistochemistry of ERBBs was obtained from the Human Protein Atlas is increased before HPA database. ERBBs genes expression and mutation analysis in cutaneous melanoma from the cBioPortal. Functional annotation and Kyoto Encyclopedia of Genes and Genomes is increased before KEGG pathway enrichment analysis from the Metascape. Correlations between ERBBs and 31 genes that were close to each other and frequently altered were explored by GEPIA. Using the GEPIA database, we also investigated the relationship between ERBBs and myeloid-derived suppressor cells (MDSC) in cutaneous melanoma. The disease-free survival and different tumor stages of ERBBs were evaluated by GEPIA. The correlation of ERBBs and tumor-infiltrating immune cells and prognostic(5 years survival rates) was tested by the Tumor Immune Estimation Resource (TIMER).ResultsIn general, the expression levels of ERBB1/2 in cutaneous melanoma were lower than those in normal skin tissue. By contrast, the ERBB3 expression level was higher in cutaneous melanoma than in normal skin tissue. Low expression of ERBB1/2 and high expression of ERBB3 were detrimental to the 5 years survival of cutaneous melanoma patients (ERBB1: log-rank P: 0.03; ERBB2: log-rank P: 0.008; ERBB3: log-rank P: 0.039). ERBB4 expression may not affect the prognosis of patients with cutaneous melanoma. ERBBs may not play a role in the tumor stage and disease-free survival in cutaneous melanoma patients. The relationship between the ERBB family and 31 genes that were close to each other and frequently altered is demonstrated as the genes regulated by the ERBB family being mainly concentrated in the RAS/RAF/MEK/ERK signaling pathway. ERBB2 can induce infiltration of CD8+ T cells and B cells, while ERBB3 can induce infiltration of CD4+ T cells, CD8+ T cells, and Neutrophil cells. ERBBs are more significantly associated with M1 macrophages, dendritic cells, Th1, Th2, Th17, and Treg cellular immune markers (Cor > 0.2). ERBB2/3 were related to MDSC in cutaneous melanoma, including human mononuclear myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), and may influence the progression of cutaneous melanoma through MDSC, but the conclusion needs further probing.ConclusionThis study investigated the prognosis and immune infiltration of the ERBB family in cutaneous melanoma. Our results suggest that ERBB1/2/3 may serve as early prognostic markers and potential therapeutic targets in cutaneous melanoma.

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Identification of hub genes in colorectal cancer based on weighted gene co-expression network analysis

Bioscience Reports ◽

10.1042/bsr20211280 ◽

2021 ◽

Author(s):

Yu Zhang ◽

Jia Luo ◽

Zhe Liu ◽

Xudong Liu ◽

Ying Ma ◽

...

Keyword(s):

Colorectal Cancer ◽

Network Analysis ◽

Ion Homeostasis ◽

Therapeutic Targets ◽

The Cancer Genome Atlas ◽

Hub Genes ◽

Oxysterol Binding Protein ◽

Interactive Analysis ◽

Kaplan Meier ◽

Novel Biomarkers

Colorectal cancer (CRC) is one of the most common tumors worldwide and is associated with high mortality. Here we performed bioinformatics analysis, which we validated using immunohistochemistry in order to search for hub genes that might serve as biomarkers or therapeutic targets in CRC. Based on data from the Cancer Genome Atlas, we identified 4,832 genes differentially expressed between CRC and normal samples (1,562 up-regulated and 3,270 down-regulated in CRC). Gene ontology analysis showed that up-regulated genes were enriched mainly in organelle fission, cell cycle regulation, and DNA replication; down-regulated genes were enriched primarily in the regulation of ion transmembrane transport and ion homeostasis. Weighted gene co-expression network analysis identified eight gene modules that were associated with clinical characteristics of CRC patients, including brown and blue modules that were associated with cancer onset. Analysis of the latter two hub modules revealed the following six hub genes: adhesion G protein-coupled receptor B3 (BAI3, also known as ADGRB3), cyclin F (CCNF), cytoskeleton-associated protein 2 like (CKAP2L), diaphanous related formin 3 (DIAPH3), oxysterol binding protein-like 3 (OSBPL3), and RERG-like protein (RERGL). Expression levels of these hub genes were associated with prognosis, based on Kaplan-Meier survival analysis of data from the Gene Expression Profiling Interactive Analysis database. Immunohistochemistry of CRC tumor tissues confirmed that OSBPL3 is up-regulated in CRC. Our findings suggest that CCNF, DIAPH3, OSBPL3, and RERGL may be useful as therapeutic targets against CRC. BAI3 and CKAP2L may be novel biomarkers of the disease.

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Comprehensive analysis and identification of key genes and signaling pathways in the occurrence and metastasis of cutaneous melanoma

PeerJ ◽

10.7717/peerj.10265 ◽

2020 ◽

Vol 8 ◽

pp. e10265

Author(s):

Hanying Dai ◽

Lihuang Guo ◽

Mingyue Lin ◽

Zhenbo Cheng ◽

Jiancheng Li ◽

...

Keyword(s):

Gene Expression ◽

Cutaneous Melanoma ◽

Metabolic Pathways ◽

Kegg Pathway ◽

Normal Skin ◽

Primary Melanoma ◽

Ppi Network ◽

Hub Genes ◽

Structural Molecule Activity ◽

Geo Database

Background Melanoma is a malignant tumor of melanocytes, and the incidence has increased faster than any other cancer over the past half century. Most primary melanoma can be cured by local excision, but metastatic melanoma has a poor prognosis. Cutaneous melanoma (CM) is prone to metastasis, so the research on the mechanism of melanoma occurrence and metastasis will be beneficial to diagnose early, improve treatment, and prolong life survival. In this study, we compared the gene expression of normal skin (N), primary cutaneous melanoma (PM) and metastatic cutaneous melanoma (MM) in the Gene Expression Omnibus (GEO) database. Then we identified the key genes and molecular pathways that may be involved in the development and metastasis of cutaneous melanoma, thus to discover potential markers or therapeutic targets. Methods Three gene expression profiles (GSE7553, GSE15605 and GSE46517) were downloaded from the GEO database, which contained 225 tissue samples. R software identified the differentially expressed genes (DEGs) between pairs of N, PM and MM samples in the three sets of data. Subsequently, we analyzed the gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the DEGs, and constructed a protein-protein interaction (PPI) network. MCODE was used to seek the most important modules in PPI network, and then the GO function and KEGG pathway of them were analyzed. Finally, the hub genes were calculated by the cytoHubba in Cytoscape software. The Cancer Genome Atlas (TCGA) data were analyzed using UALCAN and GEPIA to validate the hub genes and analyze the prognosis of patients. Results A total of 134, 317 and 147 DEGs were identified between N, PM and MM in pair. GO functions and KEGG pathways analysis results showed that the upregulated DEGs mainly concentrated in cell division, spindle microtubule, protein kinase activity and the pathway of transcriptional misregulation in cancer. The downregulated DEGs occurred in epidermis development, extracellular exosome, structural molecule activity, metabolic pathways and p53 signaling pathway. The PPI network obtained the most important module, whose GO function and KEGG pathway were enriched in oxidoreductase activity, cell division, cell exosomes, protein binding, structural molecule activity, and metabolic pathways. 14, 18 and 18 DEGs were identified respectively as the hub genes between N, PM and MM, and TCGA data confirmed the expression differences of hub genes. In addition, the overall survival curve of hub genes showed that the differences in these genes may lead to a significant decrease in overall survival of melanoma patients. Conclusions In this study, several hub genes were found from normal skin, primary melanoma and metastatic melanoma samples. These hub genes may play an important role in the production, invasion, recurrence or death of CM, and may provide new ideas and potential targets for its diagnosis or treatment.

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The Relationship between Governance Networks and Social Networks: Progress, Problems and Prospects

Political Studies Review ◽

10.1177/1478929917713952 ◽

2017 ◽

Vol 16 (4) ◽

pp. 331-341 ◽

Cited By ~ 4

Author(s):

Gaby Ramia ◽

Roger Patulny ◽

Greg Marston ◽

Kyla Cassells

Keyword(s):

Social Network ◽

Social Network Analysis ◽

Network Analysis ◽

Dark Side ◽

The Social ◽

Power Differentials ◽

Governance Networks ◽

The Difference ◽

The Relationship

A governance networks literature that uses social network analysis has emerged, but research tends to be more technical than conceptual. This restricts its accessibility and usefulness for non-quantitative scholars and practitioners alike. Furthermore, the literature has not adequately appreciated the importance of informal networking for the effective operation of governance networks. This can hinder inter-disciplinary analysis. Through a critical review, this article identifies four areas of challenge for the governance networks literature and offers four corresponding, complementary sets of concepts from the social network analysis field: (a) the difference between policy networks and governance networks, (b) the role and status of people in governance networks, (c) the ‘dark side’ of networks and the role of power differentials within them and (d) network evaluation and the question of ‘what works’ in network management. The article argues that a less technical, more accessible account of social network analysis offers an additional lens through which to view governance networks.

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Network Analysis of the Potential Role of DNA Methylation in the Relationship between Plasma Carotenoids and Lipid Profile

Nutrients ◽

10.3390/nu11061265 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1265 ◽

Cited By ~ 3

Author(s):

Bénédicte L. Tremblay ◽

Frédéric Guénard ◽

Benoît Lamarche ◽

Louis Pérusse ◽

Marie-Claude Vohl

Keyword(s):

Dna Methylation ◽

Network Analysis ◽

Lipid Profile ◽

Gene Clusters ◽

Phenotypic Traits ◽

Total Carotenoid ◽

Hub Genes ◽

The Impact ◽

The Relationship

Variability in plasma carotenoids may be attributable to several factors including genetic variants and lipid profile. Until now, the impact of DNA methylation on this variability has not been widely studied. Weighted gene correlation network analysis (WGCNA) is a systems biology method used for finding gene clusters (modules) with highly correlated methylation levels and for relating them to phenotypic traits. The objective of the present study was to examine the role of DNA methylation in the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA in 48 healthy subjects. Genome-wide DNA methylation levels of 20,687 out of 472,245 CpG sites in blood leukocytes were associated with total carotenoid concentrations. Using WGCNA, nine co-methylation modules were identified. A total of 2734 hub genes (17 unique top hub genes) were potentially related to lipid profile. This study provides evidence for the potential implications of gene co-methylation in the relationship between plasma carotenoids and lipid profile. Further studies and validation of the hub genes are needed.

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Transcriptional landscape of cholangiocarcinoma revealed by weighted gene coexpression network analysis

Briefings in Bioinformatics ◽

10.1093/bib/bbaa224 ◽

2020 ◽

Cited By ~ 1

Author(s):

Junyu Long ◽

Shan Huang ◽

Yi Bai ◽

Jinzhu Mao ◽

Anqiang Wang ◽

...

Keyword(s):

Network Analysis ◽

Clinical Characteristics ◽

Molecular Therapy ◽

Coexpression Network ◽

Gene Coexpression Network ◽

Tumor Differentiation ◽

Hub Genes ◽

Gene Coexpression ◽

The Relationship ◽

Coexpression Network Analysis

Abstract Cholangiocarcinoma (CCA) is a type of cancer with limited treatment options and a poor prognosis. Although some important genes and pathways associated with CCA have been identified, the relationship between coexpression and phenotype in CCA at the systems level remains unclear. In this study, the relationships underlying the molecular and clinical characteristics of CCA were investigated by employing weighted gene coexpression network analysis (WGCNA). The gene expression profiles and clinical features of 36 patients with CCA were analyzed to identify differentially expressed genes (DEGs). Subsequently, the coexpression of DEGs was determined by using the WGCNA method to investigate the correlations between pairs of genes. Network modules that were significantly correlated with clinical traits were identified. In total, 1478 mRNAs were found to be aberrantly expressed in CCA. Seven coexpression modules that significantly correlated with clinical characteristics were identified and assigned representative colors. Among the 7 modules, the green and blue modules were significantly related to tumor differentiation. Seventy-eight hub genes that were correlated with tumor differentiation were found in the green and blue modules. Survival analysis showed that 17 hub genes were prognostic biomarkers for CCA patients. In addition, we found five new targets (ISM1, SULT1B1, KIFC1, AURKB and CCNB1) that have not been studied in the context of CCA and verified their differential expression in CCA through experiments. Our results not only promote our understanding of the relationship between the transcriptome and clinical data in CCA but will also guide the development of targeted molecular therapy for CCA.

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Comparison of In-the-Ear and Over-the-Ear Hearing Aid Fittings

Journal of Speech and Hearing Disorders ◽

10.1044/jshd.5104.362 ◽

1986 ◽

Vol 51 (4) ◽

pp. 362-369 ◽

Cited By ~ 4

Author(s):

Donna M. Risberg ◽

Robyn M. Cox

Keyword(s):

Hearing Aids ◽

High Frequency ◽

Comparative Evaluation ◽

Speech Intelligibility ◽

Hearing Aid ◽

Hearing Aid Fitting ◽

The Difference ◽

Functional Gain ◽

The Relationship

A custom in-the-ear (ITE) hearing aid fitting was compared to two over-the-ear (OTE) hearing aid fittings for each of 9 subjects with mild to moderately severe hearing losses. Speech intelligibility via the three instruments was compared using the Speech Intelligibility Rating (SIR) test. The relationship between functional gain and coupler gain was compared for the ITE and the higher rated OTE instruments. The difference in input received at the microphone locations of the two types of hearing aids was measured for 10 different subjects and compared to the functional gain data. It was concluded that (a) for persons with mild to moderately severe hearing losses, appropriately adjusted custom ITE fittings typically yield speech intelligibility that is equal to the better OTE fitting identified in a comparative evaluation; and (b) gain prescriptions for ITE hearing aids should be adjusted to account for the high-frequency emphasis associated with in-the-concha microphone placement.

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