Determining the link between psoriasis and Crohn's disease using bioinformatics and systems biology approaches

doi:10.21203/rs.3.rs-4131605/v1

Download PDF

Article

Determining the link between psoriasis and Crohn's disease using bioinformatics and systems biology approaches

https://doi.org/10.21203/rs.3.rs-4131605/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Psoriasis, like Crohn's Disease is a lasting inflammatory condition with a complex mix of genetic and immune factors. It brings challenges to patients worldwide. This research delves into their connection by using RNA sequencing techniques and gene expression analysis to uncover genetic pathways. It emphasizes the significance of NAMPT as a gene influencing how they regulate responses and disease development. The study sheds light on the interplay among psoriasis and Crohn's disease by merging datasets. It provides perspectives, on targeted treatment approaches. Improved diagnostic accuracy.

Biological sciences/Computational biology and bioinformatics

Biological sciences/Biological techniques/Bioinformatics

Psoriasis, a skin condition characterized by raised scaly patches, is a global ailment¹. It impacts people of all age groups². Poses challenges, for both individuals and society. Various research studies have suggested that a combination of predisposition and infections^2,3 can contribute to the development of this condition. However the precise mechanisms underlying its onset remain incompletely elucidated⁴.

Crohn's disease is a inflammatory bowel disease⁵ that can affect any part of the intestinal mucosa⁶, but the most common site is at the end of the ileum^5,7. Reports in recent years indicate that the incidence of the disease is rapidly increasing⁸. The disease is a proliferative lesion⁵ throughout all layers⁹ of the bowel wall that can invade the mesentery¹⁰ and the local lymph nodes¹¹ of the bowel and is characterized by immune-mediated chronic inflammation¹². Despite extensive research, the definitive pathogenic mechanisms are not fully understood^5,13.

The medical field has long been interested, in the connections between inflammatory conditions. Research studies have indicated that individuals with psoriasis have a likelihood of developing Crohn's disease¹⁴ indicating a link between the two conditions. Furthermore genome-wide association studies (GWAS) have found connections between these diseases¹⁵. The discovery of factors implies that psoriasis and Crohn's disease may share a genetic predisposition^15,16. However more research is needed to understand the biomarkers and mechanisms involved.

In our research we examined RNA sequencing data from databases by using a method called weighted gene co network analysis (WGCNA) to pinpoint important genes related to the development of these two illnesses. These identified genes underwent verification, with datasets to enhance the reliability of our results. Then we assessed the capability of these genes using receiver operating characteristic curves (ROCs). Through genome enrichment analysis (GSEA) we uncovered the mechanisms governed by these genes while the CIBERSORT algorithm shed light on how these genes contribute to the progression of diseases by estimating their relationship, with immune cell levels in tissues.

In summary, this study screens for molecular marks and their mechanisms of actions that may play a similar role in the pathogenesis psoriasis or Crohn's. This study may help us better understand these diseases, and provide new insights and ideas for future studies on the diagnosis and treatment.

Data collection and source

GEO (http://www.ncbi.nlm.nih.gov/geo)¹⁷ is a public functional genomics data repository that accepts MIAME-compliant data submissions, including array- and sequence-based data. We conducted a search for gene expression datasets related to Crohn's disease and psoriasis. The dataset GSE114286¹⁸ contains total RNA sequences from 9 healthy volunteers and 18 patients with psoriasis vulgaris. The dataset GSE95095¹⁹ comprises 24 samples from individuals with Crohn's disease (CD) and 12 samples from healthy controls (Table S1). It is important to note that all test specimens were obtained from humans.

Co-expression network construction by WGCNA

BiocManager (version 3.16) was used to download WGCNA²⁰ (version 3.2.1), which is needed for the construction of co-expression networks. Pearson's correlation matrices and the average linkage were performed first for all pairwise genes. C_mn You can use the soft-thresholding parameter b to highlight strong correlations and penalize those with weak correlations. After selecting powers of 3 and 4, the adjacency matrixes were transformed into TOPOLOGICAL MATIXES (TOM). The TOM measures the network connectivity of a gene. It is defined by the sum of its adjacency with all other genes, in terms of network gene proportion. The dissimilarity (1-TOM) was calculated. We used the TOM based measure of dissimilarity in order to perform average linkage hierarchy grouping to classify genes with similar expression profiles. The minimum size for the gene group was 30. To analyze the modules, we calculated the dissimilarity of the module eigen genes, selected a cut line for the module dendrogram, and merged some modules.

Validation of Hub Gene Expression

The expression levels of the hub genes were validated in two datasets, GSE182740 for psoriasis and GSE52746²¹ for Crohn's disease (CD). GSE182740 included 9 samples from psoriasis patients and 6 control samples, while GSE52746 included 10 samples from patients with Crohn's disease (CD) and 17 control samples. The comparison between the two datasets was conducted using an independent t-test, and statistical significance was defined as a p-value of < 0.05.

Receiver Operating Characteristic Curves

Using the pROC²² package in R language to generate subject operating characteristic (ROC) curves to evaluate the predictive accuracy of hub genes.

Analysis of immune cell infiltration on hub genes

The research employed CIBERSORT²³ algorithms to examine RNA sequencing data from groups of individuals diagnosed with Crohn's disease and psoriasis. The aim was to determine the ratios of 22 immune infiltrating cells and to conduct correlation analyses, between gene expression and immune cell compositions. A p value < 0.05 was deemed significant in terms.

Enrichment analysis

The Kyoto Encyclopedia of Genes and Genomes (KEGG)²⁴ pathway analysis of the expression of the two hub genes was performed using the R Cluster Profiler program²⁵ (version 4.2.2). Enriched pathways were identified with a significance threshold of P < 0.05 and a false discovery rate (FDR) value of 0.25.

Construction of Co-Expression Network and Identification of hub Genes

The flow chart of this study is shown in (Fig. 1). We performed a Weighted Gene Co-expression Network Analysis (WGCNA) on the psoriasis dataset (GSE114286) and the Crohn's disease dataset (GSE95095) to identify genes commonly influencing both diseases. Soft-thresholding powers of 3 and 4 were chosen using hierarchical clustering to meet the scale-free network criteria. This method resulted in 15 and 45 co-expression modules for each disease, respectively, with the cyan and purple modules showing the strongest association with disease pathogenesis. Following this, 11 genes overlapping between the cyan and purple modules were chosen for additional analysis (Fig. 2).

Validation of Hub Genes

Validation was conducted using psoriasis (GSE182740) and Crohn's Disease (CD) (GSE52746) datasets obtained from the GEO database. The results indicated that two hub genes(NAMPT and CXCR2)were significantly upregulated in both Crohn's Disease (CD) and psoriasis (Pso) compared to normal tissues (Fig. 3).

Analysis of immune cell infiltration

This analysis included quantifying 22 types of immune cells (Table S2), which are illustrated in stacked bar graphs (Fig. 4A-B). We then used Spearman's analysis to determine the relationship between two hub genes, and 22 types of immune cell. Figure 5A shows that CXCR2 was positively correlated with the infiltrations of memory CD4T cells and neutrophils. NAMPT showed a positive correlation with the infiltrations of memory CD4T cells, neutrophils and monocytes. This is shown in Figs. 5B. These analyses highlight the pivotal role hub genes play in immune cell infiltration. This implies their critical involvement in disease development and progression.

GSEA Results of Hub Genes

Gene Set Enrichment Analysis was performed to identify pathways that are regulated differently by high and low expression groups.(Table S3) The results showed a strong correlation between activation of "NOD-like signaling pathways" "TOLL signaling pathways" "JAK STAT signaling pathways" and increased CXCR2 expression in both GSE114286 datasets and GSE95095 (Fig. 6A). Moreover, higher expressions NAMPT were associated with the activation of "NOD-like signaling pathway", "P53 signaling pathways" and "NOD receptor signaling pathways" in both datasets (Fig. 6B).

Diagnostic efficacy of signature genes in psoriasis and Crohn's disease

The identified signature genes exhibited elevated expression in samples from psoriasis and Crohn's disease patients compared to healthy controls, indicating their potential involvement in the pathogenesis of both conditions. In an external validation cohort, the diagnostic efficacy of each signature gene for psoriasis and Crohn's disease was assessed. Figure 7 presents the area under the curve (AUC) of the receiver operating characteristic (ROC) for these genes.

In this study, public databases were used to identify common hub genes and pathways in Crohn's disease and psoriasis using bioinformatics.Validation was performed using external datasets. Significantly, CXCR2 and NAMPT were upregulated in Crohn's disease and psoriasis patients, indicating their role as hub genes. They showed notable associations with CD4 memory T cells and neutrophils. Furthermore, NAMPT exhibited a notable correlation with monocytes. GSEA revealed a strong link between the high expression of these hub genes and the P53 and NOD-like signaling pathways. Consequently, CXCR2 and NAMPT are likely to have a substantial impact on Crohn's disease and psoriasis through their modulation of CD4 memory T cell and neutrophil activities.

CXCR2, a gene belonging to the chemokine receptor subfamily of the G protein-coupled receptor (GPCR) family²⁶, This family comprises transmembrane proteins²⁷ that transmit external cellular signals internally. CXCR2 shows a high affinity for C-X-C chemokines like IL-8²⁸, crucial for regulating immune cells²⁹, especially neutrophils. CXCR2 primarily functions as a chemokine receptor³⁰, directing immune cells, notably neutrophils, to inflammation or infection sites. This migration occurs through the recognition and binding of specific chemokines, predominantly IL-8 (CXCL8). Neutrophils are the first line of defence against getting infected and inflamed³¹;CXCR2 is crucial in regulating their migration. In addition to attracting immune cells to inflammation sites, CXCR2 also affects their activity²⁹. For example, activation of CXCR2 increases neutrophil production of reactive oxygen species³² (ROS) and release of inflammatory factors, crucial for pathogen elimination³³ and immune response modulation. Increased CXCR2 expression and activity have been observed in several inflammation-related diseases, including COPD³⁴, asthma³⁵, psoriasis³⁶, and some cancers. The uncontrolled inflammatory response characteristic of these diseases suggests CXCR2 as a potential therapeutic target. Recent studies show that CXCR2 plays a critical role in neutrophil aggregation³⁷ during the development of ImQ-induced psoriasis lesions³⁸. Research shows that drugs targeting CXCR2 can help decrease the influx of neutrophils³⁹, which in turn can lessen the severity of bowel disease⁴⁰ (IBD). This indicates that inhibiting CXCR2 could be an approach, for managing and treating psoriasis and Crohns disease.

NAMPT plays a role, in biological functions such as cellular energy production⁴¹, DNA repair⁴², aging processes⁴³, immune system activities⁴⁴ and inflammation regulation⁴³. This enzyme is crucial for the synthesis of nicotinamide adenine dinucleotide^43,45 (NAD+) which's a coenzyme in cells. NAD + is central to metabolism as it acts as a cofactor for enzymes involved in energy generation DNA repair mechanisms, genetic regulation and cell signaling pathways⁴⁶. NAMPTs impact on the system is significant because NAD + plays a role in both cellular metabolism and regulating immune cell functions. Notably NAD + influences the differentiation and activation of T cells⁴⁷ thereby affecting responses. Moreover when released cells NAMPT acts as a cytokine⁴⁸ during reactions. In this capacity NAMPT triggers the activation of cells by binding to receptors⁴⁹ leading to the release of inflammatory factors and contributing to inflammation processes. Studies indicate that the modulation of NAD + metabolism by NAMPT enhances skin immunity responses^50,51 in conditions, like psoriasis. Another study suggest NAMPT's role in Crohn's disease⁵². NAMPT is a key gene in both psoriasis and Crohn's disease. The recruitment of neutrophils, CD4 memory T cells, and monocytes might be a common mechanism in psoriasis and Crohn's disease pathogenesis.

The study has some limitations. First, the two key genes identified were only validated in the data set, lacking validation in cellular and animal models. However, the roles of NAMPT and CXCR2 in CD and PSO have been elucidated in multiple preclinical and clinical studies, reflecting the reliability of this study. Follow-up studies should include the above two levels of experimental validation. Second, validation of central genes and key pathways was performed in datasets of patients with Crohn's disease and psoriasis, respectively, and not in datasets of patients with both diseases. This aspect of validation is incomplete due to the lack of data sets for patients with both conditions. Follow-up studies should focus on collecting skin lesions and intestinal mucosa samples from patients with both diseases.

Funding

the General project of Chongqing Nature Science Foundation [No. cstc2021jcyj-msxmX0283].

Competing interests

The authors declare no competing interests.

Author contributions

These authors contributed equally: Shihao Xu and Ya Li

S.H.X: Conceptualization, methodology, and writing-original draft. L.Y: resources, data curation and writing-review and editing. X.Y: data collection and software. C.Z.X and K.H: data collection, and methodology. Z.Q.W: resources, software, conceptualization, writing-review and editing.

Authors and Affiliations

The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuanjiagang, Chongqing, 400016, People’s Republic of China

Zhengqiang Wei , Shihao Xu, Ya Li, Xin Yang, ChaoZheng Xie & Kuan He

Data availability

The raw data supporting the conclusions of this article will be made available by the corresponding author (email address: [email protected]) without undue reservation.

Griffiths, C. E. M., Armstrong, A. W., Gudjonsson, J. E. & Barker, J. Psoriasis. Lancet 397, 1301–1315 (2021). https://doi.org:10.1016/s0140-6736(20)32549-6
Griffiths, C. E. & Barker, J. N. Pathogenesis and clinical features of psoriasis. Lancet 370, 263–271 (2007). https://doi.org:10.1016/s0140-6736(07)61128-3
Chen, L. & Tsai, T. F. HLA-Cw6 and psoriasis. Br J Dermatol 178, 854–862 (2018). https://doi.org:10.1111/bjd.16083
Veale, D. J. & Fearon, U. The pathogenesis of psoriatic arthritis. Lancet 391, 2273–2284 (2018). https://doi.org:10.1016/s0140-6736(18)30830-4
Torres, J., Mehandru, S., Colombel, J. F. & Peyrin-Biroulet, L. Crohn's disease. Lancet 389, 1741–1755 (2017). https://doi.org:10.1016/s0140-6736(16)31711-1
El-Nakeep, S., Shawky, A., Abbas, S. F. & Abdel Latif, O. Stem cell transplantation for induction of remission in medically refractory Crohn's disease. Cochrane Database Syst Rev 5, Cd013070 (2022). https://doi.org:10.1002/14651858.CD013070.pub2
Chongthammakun, V., Fialho, A., Fialho, A., Lopez, R. & Shen, B. Correlation of the Rutgeerts score and recurrence of Crohn's disease in patients with end ileostomy. Gastroenterol Rep (Oxf) 5, 271–276 (2017). https://doi.org:10.1093/gastro/gow043
Roda, G. et al. Crohn's disease. Nat Rev Dis Primers 6, 22 (2020). https://doi.org:10.1038/s41572-020-0156-2
Yang, Z., Xu, X., Dong, Y. & Zhang, Y. The pathological and outcome characteristics of renal lesions in Crohn's disease. BMC Nephrol 23, 256 (2022). https://doi.org:10.1186/s12882-022-02883-8
Rivera, E. D., Coffey, J. C., Walsh, D. & Ehrenpreis, E. D. The Mesentery, Systemic Inflammation, and Crohn's Disease. Inflamm Bowel Dis 25, 226–234 (2019). https://doi.org:10.1093/ibd/izy201
van der Does de Willebois, E. M. L. Mesenteric SParIng versus extensive mesentereCtomY in primary ileocolic resection for ileocaecal Crohn's disease (SPICY): study protocol for randomized controlled trial. BJS Open 6 (2022). https://doi.org:10.1093/bjsopen/zrab136
Yuan, Y., Fu, M., Li, N. & Ye, M. Identification of immune infiltration and cuproptosis-related subgroups in Crohn's disease. Front Immunol 13, 1074271 (2022). https://doi.org:10.3389/fimmu.2022.1074271
Melton, S. L., Taylor, K. M., Gibson, P. R. & Halmos, E. P. Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease. Aliment Pharmacol Ther 57, 932–947 (2023). https://doi.org:10.1111/apt.17451
Sandborn, W. J. et al. Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study. Gastroenterology 162, 1650–1664.e1658 (2022). https://doi.org:10.1053/j.gastro.2022.01.047
Freuer, D., Linseisen, J. & Meisinger, C. Association Between Inflammatory Bowel Disease and Both Psoriasis and Psoriatic Arthritis: A Bidirectional 2-Sample Mendelian Randomization Study. JAMA Dermatol 158, 1262–1268 (2022). https://doi.org:10.1001/jamadermatol.2022.3682
Li, Y., Guo, J., Cao, Z. & Wu, J. Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study. Front Immunol 13, 916645 (2022). https://doi.org:10.3389/fimmu.2022.916645
Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30, 207–210 (2002). https://doi.org:10.1093/nar/30.1.207
Xue, X. et al. Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing. Biosci Rep 38 (2018). https://doi.org:10.1042/bsr20180958
Wang, J. et al. Identification and validation of the common pathogenesis and hub biomarkers in Hirschsprung disease complicated with Crohn's disease. Front Immunol 13, 961217 (2022). https://doi.org:10.3389/fimmu.2022.961217
Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008). https://doi.org:10.1186/1471-2105-9-559
Leal, R. F. et al. Identification of inflammatory mediators in patients with Crohn's disease unresponsive to anti-TNFα therapy. Gut 64, 233–242 (2015). https://doi.org:10.1136/gutjnl-2013-306518
Robin, X. et al. pROC: an open-source package for R and S + to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011). https://doi.org:10.1186/1471-2105-12-77
Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods 12, 453–457 (2015). https://doi.org:10.1038/nmeth.3337
Kanehisa, M. & Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28, 27–30 (2000). https://doi.org:10.1093/nar/28.1.27
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 16, 284–287 (2012). https://doi.org:10.1089/omi.2011.0118
Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018 (2008). https://doi.org:10.1016/j.cell.2008.03.038
Pawlik, K. & Mika, J. Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain. Molecules 28 (2023). https://doi.org:10.3390/molecules28155766
Korbecki, J. et al. CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer. Int J Mol Sci 23 (2022). https://doi.org:10.3390/ijms23042168
Liao, W. et al. KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer. Cancer Cell 35, 559–572.e557 (2019). https://doi.org:10.1016/j.ccell.2019.02.008
Liu, K. et al. Structural basis of CXC chemokine receptor 2 activation and signalling. Nature 585, 135–140 (2020). https://doi.org:10.1038/s41586-020-2492-5
Nourshargh, S. & Alon, R. Leukocyte migration into inflamed tissues. Immunity 41, 694–707 (2014). https://doi.org:10.1016/j.immuni.2014.10.008
Jiao, Y. et al. Exosomal PGE2 from M2 macrophages inhibits neutrophil recruitment and NET formation through lipid mediator class switching in sepsis. J Biomed Sci 30, 62 (2023). https://doi.org:10.1186/s12929-023-00957-9
Adrover, J. M. et al. A Neutrophil Timer Coordinates Immune Defense and Vascular Protection. Immunity 50, 390–402.e310 (2019). https://doi.org:10.1016/j.immuni.2019.01.002
Pedersen, F. et al. Neutrophil extracellular trap formation is regulated by CXCR2 in COPD neutrophils. Eur Respir J 51 (2018). https://doi.org:10.1183/13993003.00970-2017
Ha, H., Debnath, B. & Neamati, N. Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics 7, 1543–1588 (2017). https://doi.org:10.7150/thno.15625
Chen, L. et al. DZ2002 alleviates psoriasis-like skin lesions via differentially regulating methylation of GATA3 and LCN2 promoters. Int Immunopharmacol 91, 107334 (2021). https://doi.org:10.1016/j.intimp.2020.107334
Wang, H. et al. KIAA1199 drives immune suppression to promote colorectal cancer liver metastasis by modulating neutrophil infiltration. Hepatology 76, 967–981 (2022). https://doi.org:10.1002/hep.32383
Sumida, H. et al. Interplay between CXCR2 and BLT1 facilitates neutrophil infiltration and resultant keratinocyte activation in a murine model of imiquimod-induced psoriasis. J Immunol 192, 4361–4369 (2014). https://doi.org:10.4049/jimmunol.1302959
Sharma, B., Nawandar, D. M., Nannuru, K. C., Varney, M. L. & Singh, R. K. Targeting CXCR2 enhances chemotherapeutic response, inhibits mammary tumor growth, angiogenesis, and lung metastasis. Mol Cancer Ther 12, 799–808 (2013). https://doi.org:10.1158/1535-7163.Mct-12-0529
Boppana, N. B. et al. Blockade of CXCR2 signalling: a potential therapeutic target for preventing neutrophil-mediated inflammatory diseases. Exp Biol Med (Maywood) 239, 509–518 (2014). https://doi.org:10.1177/1535370213520110
Zhu, Y., Liu, J., Park, J., Rai, P. & Zhai, R. G. Subcellular compartmentalization of NAD(+) and its role in cancer: A sereNADe of metabolic melodies. Pharmacol Ther 200, 27–41 (2019). https://doi.org:10.1016/j.pharmthera.2019.04.002
Navas, L. E. & Carnero, A. NAD(+) metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther 6, 2 (2021). https://doi.org:10.1038/s41392-020-00354-w
Garten, A. et al. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11, 535–546 (2015). https://doi.org:10.1038/nrendo.2015.117
Ratnayake, D. et al. Macrophages provide a transient muscle stem cell niche via NAMPT secretion. Nature 591, 281–287 (2021). https://doi.org:10.1038/s41586-021-03199-7
Gong, H. et al. miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD(+)/SIRT inactivation. Signal Transduct Target Ther 7, 66 (2022). https://doi.org:10.1038/s41392-022-00886-3
Chini, C. C. S., Zeidler, J. D., Kashyap, S., Warner, G. & Chini, E. N. Evolving concepts in NAD(+) metabolism. Cell Metab 33, 1076–1087 (2021). https://doi.org:10.1016/j.cmet.2021.04.003
Wang, Y. et al. NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells. Cell Rep 36, 109516 (2021). https://doi.org:10.1016/j.celrep.2021.109516
Yao, H. et al. Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and their preclinical neuroprotective activity. Cell Res 32, 570–584 (2022). https://doi.org:10.1038/s41422-022-00651-9
Yang, L. et al. Nicotine rebalances NAD(+) homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity. Nat Commun 14, 900 (2023). https://doi.org:10.1038/s41467-023-36543-8
Mercurio, L. et al. Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits. Int J Mol Sci 22 (2021). https://doi.org:10.3390/ijms22136860
Indini, A., Fiorilla, I., Ponzone, L., Calautti, E. & Audrito, V. NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets. Int J Mol Sci 23 (2022). https://doi.org:10.3390/ijms23179985
Neubauer, K. et al. Oversecretion and Overexpression of Nicotinamide Phosphoribosyltransferase/Pre-B Colony-Enhancing Factor/Visfatin in Inflammatory Bowel Disease Reflects the Disease Activity, Severity of Inflammatory Response and Hypoxia. Int J Mol Sci 20 (2019). https://doi.org:10.3390/ijms20010166

No competing interests reported.

SupplementaryInformation.xlsx
Table S1: Summary of included studies. Table S2: Relative classification of immune cells. Table S3: Results of GSEA enrichment analyses.

Download PDF

Version 1

posted

You are reading this latest preprint version

Determining the link between psoriasis and Crohn's disease using bioinformatics and systems biology approaches

Status:

Version 1

Abstract

Figures

Introduction

Materials and methods

Data collection and source

Co-expression network construction by WGCNA

Validation of Hub Gene Expression

Receiver Operating Characteristic Curves

Analysis of immune cell infiltration on hub genes

Enrichment analysis

Results

Construction of Co-Expression Network and Identification of hub Genes

Validation of Hub Genes

Analysis of immune cell infiltration

GSEA Results of Hub Genes

Diagnostic efficacy of signature genes in psoriasis and Crohn's disease

Discussion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1