Blood Gene Expression Profiles Research Articles

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia

BackgroundFibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status.MethodsThe peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model.ResultsThe patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer–Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable.ConclusionMicro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms.

The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis. Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well. Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes. Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05). We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.

Transcriptomic signature related to poor welfare of sport horses

The improvement of horse welfare through housing conditions has become a real issue in recent years and have highlighted the detrimental effect of individual housing of horses on their health and behaviour. In this new study, we analysed the blood transcriptome of 45 sport horses housed individually that were previously examined for their behaviour and gut microbiota. We performed differential and regression analyses of gene expression, followed by downstream bioinformatic analyses, to unveil the molecular pathways related to the behavioural changes associated with welfare impairment in these sport horses. We found that aggressiveness towards humans was the behavioural indicator the most correlated to blood gene expression and that the pathways involved belonged mainly to systemic inflammation. In contrast, the correlations between genes, alert postures and unresponsiveness towards the environment were weak. When blood gene expression profiling was combined with faecal microbiota of a sub-population of horses, stereotypies came out as the most correlated to blood gene expression. This study shows that aggressiveness towards humans and stereotypies are behavioural indicators that covary with physiological alterations. Further studies are needed regarding the biological correlates of unresponsiveness to the environment and alert postures.

Differential Expression of Insulin Resistance Genes in Polycystic Ovary Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a common hormonal disorder worldwide among women of reproductive age. It is characterized by endocrine, reproductive, and metabolic abnormalities. Insulin resistance (IR) is one of its most important clinical features, which has been associated with metabolic disorders and increased risk of type 2 diabetes (T2D). This study aimed to explore the whole blood gene expression profiling related to IR in PCOS patients compared to controls. Methods: Blood RNA was extracted from 5 PCOS and 5 non-PCOS women with matched age and BMI. Homeostasis model assessment (HOMA-IR) was used to estimate the IR. The expression of IR genes was analyzed by Profiler PCR array. Results: Both groups have similar levels of HOMA-IR (p&gt;0.05). However, differential expression levels were observed between them. Fourteen genes were upregulated and 26 genes were downregulated in PCOS samples. Among the upregulated genes (&gt;2 fold-change, p-value&lt;0.05) are ADIPOQ, ADIPOR1, OLR, IGF-1, and APOE. Downregulated genes (&gt;-2 fold-change, p-value&lt;0.05) include HK-2, IRS1, and SERPINE1. These genes are involved in insulin and adipokines signaling, commonly dysregulated in T2D. They are also involved in innate immunity and inflammatory processes and are important for lipid and carbohydrate metabolism. Conclusion: Our finding suggests that despite both groups having no difference in IR level, there are differentially expressed genes involved in the IR pathway.

Associations of gene expression in blood with BMI and weight changes among women in the Norwegian Women and Cancer postgenome cohort.

This study aimed to evaluate associations between blood gene expression profiles and (1) current BMI and (2) past weight changes (WCs) among womenwho had never been diagnosed with cancerin the Norwegian Women and Cancer (NOWAC) postgenome cohort. This cross-sectional study (N = 1694) used gene expression profiles and information from three questionnaires: Q1 (baseline), Q2 (follow-up), and Q3 (blood collection). The authors performed gene-wise linear regression models to identify differentially expressed genes (DEGs) and functional enrichment analyses to identify their biological functions. When assessing BMIQ3 , the study observed 2394, 769, and 768 DEGs for the obesity-versus-normal weight, obesity-versus-overweight, and overweight-versus-normal weight comparisons, respectively. Up to 169 DEGs were observed when investigating WCQ3-Q1 (mean = 7 years, range = 5.5-14 years) and WCQ3-Q2 (mean = 1 year, range = <1 month-9 years) in interaction models with BMI categories, of which 1 to 169 genes were associated with WCs and 0 to 9 were associated with interaction effects of BMI and WCs. Biological functions of BMI-associated DEGs were linked to metabolism, erythrocytes, oxidative stress, and immune processes, whereas WC-associated DEGs were linked to signal transduction. Many BMI-associated but few WC-associated DEGs were identified in the blood of women in Norway. The biological functions of BMI-associated DEGs likely reflect systemic impacts of obesity, especially blood reticulocyte-erythrocyte ratio shifts.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Bioinformatic identification and experiment validation revealed that ACTG1 is a promising prognostic signature and therapeutic target for sepsis.

In the intensive care unit, sepsis is a prevalent clinical syndrome (i.e. the final pathway to death from most infections). Peripheral blood gene expression profiling is becoming more and more accepted as a potential diagnostic or prognostic tool. This work aimed to recognize genes related to sepsis, providing potential translational therapeutic targets. RNA sequencing was performed on peripheral blood mononuclear cells from 20 healthy control subjects and 51 sepsis patients. Weighted gene coexpression network analysis was employed to pick out sepsis-related and immunocyte-related gene modules. Genes in the yellow module are primarily involved in excessive inflammation and immune suppression. STRING and Cytoscape were combined to identify ACTG1 and IQGAP1 as hub genes with highest connective degree, and prognostic predication value of ACTG1 was confirmed. Both univariate and multivariate logistic regression analyses were carried out. ACTG1 messenger RNA expression was increased in animal and in cell-related sepsis models. Small interfering RNA revealed decreasing ACTG1 can reduce the in vitro sepsis model apoptosis. We have authenticated ACTG1 as a reliable signature of a poor outcome of sepsis and promising therapeutic targets for sepsis.

Gene expression profiling in whole blood stimulated ex vivo with lipopolysaccharide as a tool to predict post-stroke depressive symptoms: Proof-of-concept study.

Prediction of post-stroke depressive symptoms (DSs) is challenging in patients without a history of depression. Gene expression profiling in blood cells may facilitate the search for biomarkers. The use of an ex vivo stimulus to the blood helps to reveal differences in gene profiles by reducing variation in gene expression. We conducted a proof-of-concept study to determine the usefulness of gene expression profiling in lipopolysaccharide (LPS)-stimulated blood for predicting post-stroke DS. Out of 262 enrolled patients with ischemic stroke, we included 96 patients without a pre-stroke history of depression and not taking any anti-depressive medication before or during the first 3 months after stroke. We assessed DS at 3 months after stroke using the Patient Health Questionnaire-9. We used RNA sequencing to determine the gene expression profile in LPS-stimulated blood samples taken on day 3 after stroke. We constructed a risk prediction model using a principal component analysis combined with logistic regression. We diagnosed post-stroke DS in 17.7% of patients. Expression of 510 genes differed between patients with and without DS. A model containing 6 genes (PKM, PRRC2C, NUP188, CHMP3, H2AC8, NOP10) displayed very good discriminatory properties (area under the curve: 0.95) with the sensitivity of 0.94 and specificity of 0.85. Our results suggest the potential utility of gene expression profiling in whole blood stimulated with LPS for predicting post-stroke DS. This method could be useful for searching biomarkers of post-stroke depression.

CSL362 potently and specifically depletes pDCs in vitro and ablates SLE-immune complex-induced IFN responses

Systemic lupus erythematosus (SLE) is an autoimmune disease with significant morbidity and mortality. Type I interferon (IFN) drives SLE pathology and plasmacytoid dendritic cells (pDCs) are potent producers of IFN; however, the specific effects of pDC depletion have not been demonstrated. We show CD123 was highly expressed on pDCs and the anti-CD123 antibody CSL362 potently depleted pDCs invitro. CSL362 pre-treatment abrogated the induction of IFNα and IFN-induced gene transcription following stimulation with SLE patient-derived serum or immune complexes. RNA transcripts induced in pDCs by exvivo stimulation with TLR ligands were reflected in gene expression profiles of SLE blood, and correlated with disease severity. TLR ligand-induced protein production by SLE patient peripheral mononuclear cells was abrogated by CSL362 pre-treatment including proteins over expressed in SLE patient serum. These findings implicate pDCs as key drivers in the cellular activation and production of soluble factors seen in SLE.

Single cell and genomic profiling of PBMC-expanded NK cells in first-in-dog clinical trial of allogeneic adoptive NK cell therapy for dogs with cancer

Abstract Natural killer (NK) cells are innate cytotoxic cells with a crucial role in anti-tumor responses, making them a promising candidate for adoptive immunotherapy (IT). CD5 depletion was previously used to isolate CD5 dim-expressing NK cells as a source of expanded NK cells for IT, but this technique can limit the yield of the final NK product. Here, we used bulk and single cell (SC) sequencing to compare ex vivo culture conditions using standard CD5 depletion versus unmanipulated PBMCs as the source of expanded NK cells comparing transcriptomic profiles from 5 matched healthy beagle donors using both techniques and subsequently from 5 dogs with naturally occurring malignant melanoma who received allogeneic PBMC-expanded NK cells in a first-in-dog clinical trial. Notably, beagle-derived PBMC-expanded cells had upregulation of NK pathways related to activation and function compared to CD5 depleted cells, suggesting bulk PBMCs may yield a superior product. Clinically, there were no serious adverse events using PBMC-expanded allogeneic NK cells, and one dog survived 445 days post-treatment, suggesting possible clinical benefit. SC analysis of PBMCs from this dog before, during, and after treatment showed a robust NK cell population across timepoints with high expression of cytotoxicity-related genes, such as GZMB and NCR3, lasting 14 days post-NK transfer. SC data also suggested a previously uncharacterized concordance of NK and CD8 T cell gene expression profiles in canine peripheral blood. Overall, allogeneic NK transfer using PBMC-expanded NK cells appears promising in dogs with cancer, and pre-clinical and clinical data support the use of SC analysis as a valuable technique for biomarker identification and optimizing NK IT in dogs. This study was funded by the National Institutes of Health/National Cancer Institute grant U01 CA224166-01, the 3U01CA224166-02S1 and 5R03CA252793-02 grants, and the V Foundation Victory over Cancer through the Canter Laboratory. Student support was provided by the AVMA/AVMF 2nd Opportunity Summer Research Scholarship.

Acute ischemic stroke: how to investigate the association between disease etiology and gene expression profiles

Background: Acute ischemic stroke (AIS) represents one of the principal causes of neurological morbidity and mortality worldwide. For a prompt and efficient cerebral blood restoration, intravenous treatment with rt-PA is often combined with mechanical thrombectomy (MT) which provides cerebral thrombi (CT) as study material, allowing the investigation of its cellular composition, morphological and histopathological features. Indeed, the determination of stroke etiology, typically defined by the TOAST classification, is paramount for prognostic factors, outcome, and management of the event. Aim of the study is therefore to highlight and analyze gene expression profiles in thrombotic tissue and peripheral blood (PB) in the comparison between strokes of cardioembolic (CE) and atherosclerotic (LAA) origin. Methods: We performed gene expression profiles of 92 patients. CT were stored in RNA later and RNA was extracted by PAX gene blood miRNA kit. The global gene expression profile was assessed by Affymetrix technology using GeneChip Human Transcriptome Array 2.0 combined with Affymetrix Transcriptome Analysis Console (TAC) Software. Results: Currently, we focused our attention on CT data analysis. The analysis revealed a significant difference (p-value&lt;0.05 and FoldChange=2 as threshold) in gene expression when comparing LAA and CE stroke. In particular, from CT of atherosclerotic origin emerges an overexpression of 1766 genes. Prominent among them are genes such as MMP-9, TGFB, TGFBR and CXCL1, primarily involved in neutrophil-mediated immunity, Blood-Brain Barrier (BBB) disruption processes, and associated with atherosclerotic plaque instability and related to poor neurological outcome, suggesting a deleterious role in human brain injury. As concerns CE patients, 57 genes mainly involved in transcriptional regulatory processes turn out to be significantly overexpressed. Conclusions: Transcriptome profiling is a powerful weapon for revealing expression patterns associated with complex disorders. The variation of gene expression profiles confirmed and extended several known pathophysiological mechanisms and may be one way of delineating different stroke etiology.

Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation.

The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n=117 (47%), 1 Not-TX n=59 (25%) and >1 Not-TX n=64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p<.001) and more chronic changes on 1-year surveillance biopsy (p=.007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p<.001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

(1002) Differences in Individual Blood Gene Expression Profile (GEP) Levels in T-Cell Mediated Rejection Assessed by Molecular Microscopy in Heart Transplant

(1002) Differences in Individual Blood Gene Expression Profile (GEP) Levels in T-Cell Mediated Rejection Assessed by Molecular Microscopy in Heart Transplant

(104) Relation Between Individual Blood Gene Expression Profile (GEP) and Tissue GEP in Antibody-Mediated Rejection in Heart Transplant

(104) Relation Between Individual Blood Gene Expression Profile (GEP) and Tissue GEP in Antibody-Mediated Rejection in Heart Transplant

Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19

PurposeFollowing a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19.MethodsWe analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge.ResultsWe observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory CD4+ and effector CD8+ T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation.ConclusionThe lack of restoration of gene expression to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures.

Effect of Age and Sex on Gene Expression-Based Radiation Biodosimetry Using Mouse Peripheral Blood

Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24 hours later and subjected to whole-genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ±0.75 Gy (R2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex.

Peripheral Blood Gene Expression Profile of Infants with Atopic Dermatitis

To enhance the understanding of molecular mechanisms and mine previously unidentified biomarkers of pediatric atopic dermatitis, PBMC gene expression profiles were generated by RNA sequencing in infants with atopic dermatitis and age-matched controls. A total of 178 significantly differentially expressed genes (DEGs) (115 upregulations and 63 downregulations) were seen, compared with those in healthy controls. The DEGs identified included IL1β, TNF, TREM1, IL18R1, and IL18RAP. DEGs were validated by real-time RT- qPCR in a larger number of samples from PBMCs of infants with atopic dermatitis aged <12 months. Using the DAVID (Database for Annotation, Visualization and Integrated Discovery) database, functional and pathway enrichment analyses of DEGs were performed. Gene ontology enrichment analysis showed that DEGs were associated with immune responses, inflammatory responses, regulation of immune responses, and platelet activation. Pathway analysis indicated that DEGs were enriched in cytokine‒cytokine receptor interaction, immunoregulatory interactions between lymphoid and nonlymphoid cells, hematopoietic cell lineage, phosphoinositide 3-kinase‒protein kinase B signaling pathway, NK cell‒mediated cytotoxicity, and platelet activation. Furthermore, the protein‒protein interaction network was predicted using the STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database and visualized with Cytoscape software. Finally, on the basis of the protein‒protein interaction network, 18 hub genes were selected, and two significant modules were obtained. In conclusion, this study sheds light on the molecular mechanisms of pediatric atopic dermatitis and may provide diagnostic biomarkers and therapeutic targets.

Abstract WP223: Identification Of Cerebral Amyloid Angiopathy With A Leukocyte Gene Expression Profile

Introduction: Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease featuring beta-amyloid deposits within the cerebral vasculature. It is a major cause of cognitive decline and intracerebral hemorrhage in the elderly. This study evaluated whether gene expression profiles in peripheral blood can differentiate patients with CAA from vascular risk factor and healthy controls. Methods: In 27 patients with CAA blood cell gene expression was compared to 55 controls. Total RNA was isolated from PAXgene tubes and measured by RNA sequencing. Differentially expressed genes between CAA and controls were identified by ANOVA adjusting for age and sex. Functional pathway analysis identified pathways associated with CAA. A prediction model to distinguish CAA from controls was developed using linear discriminant analysis with feature selection by forward selection. Model performance was evaluated by 10-fold leave-one-out cross validation. Results: 686 differentially expressed genes were identified (p&lt;0.05, fold change &gt;|1.2|), of interest ADAM15, CAMK1D, CAP1 and TGFB1 . Canonical pathway analysis identified cell movement of phagocytes, activation of phagocytes, CREB, degranulation of leukocytes, immune response of cells, inflammatory response, and IL-23 signaling. A 24 gene panel differentiated patients with CAA from controls with &gt;95% sensitivity and specificity. The identified genes reveal differences in immune system regulation in patients with CAA compared to vascular risk factor and healthy control patients. Differences identified include a potential shift in beta-amyloid uptake by phagocytes ( TGFB1, CREB, CAMK1D ), an increase in vascular extracellular matrix disruption ( ADAM15, CAP1 ), and a possible alteration in amyloid precursor processing ( BRI3BP, SORCS3 ). Conclusion: Differences in peripheral leukocyte gene expression are present in patients with CAA compared to control patients. These relate to differences in immune activation and signaling associated with CAA. The differences in blood cell gene expression shows promise to distinguish CAA from controls, though further evaluation in larger cohorts is required to further evaluate potential diagnostic utility of this gene expression profile.

Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

Peripheral Blood Genes Crosstalk between COVID-19 and Sepsis.

Severe coronavirus disease 2019 (COVID-19) has led to a rapid increase in death rates all over the world. Sepsis is a life-threatening disease associated with a dysregulated host immune response. It has been shown that COVID-19 shares many similarities with sepsis in many aspects. However, the molecular mechanisms underlying sepsis and COVID-19 are not well understood. The aim of this study was to identify common transcriptional signatures, regulators, and pathways between COVID-19 and sepsis, which may provide a new direction for the treatment of COVID-19 and sepsis. First, COVID-19 blood gene expression profile (GSE179850) data and sepsis blood expression profile (GSE134347) data were obtained from GEO. Then, we intersected the differentially expressed genes (DEG) from these two datasets to obtain common DEGs. Finally, the common DEGs were used for functional enrichment analysis, transcription factor and miRNA prediction, pathway analysis, and candidate drug analysis. A total of 307 common DEGs were identified between the sepsis and COVID-19 datasets. Protein-protein interactions (PPIs) were constructed using the STRING database. Subsequently, hub genes were identified based on PPI networks. In addition, we performed GO functional analysis and KEGG pathway analysis of common DEGs, and found a common association between sepsis and COVID-19. Finally, we identified transcription factor-gene interaction, DEGs-miRNA co-regulatory networks, and protein-drug interaction, respectively. Through ROC analysis, we identified 10 central hub genes as potential biomarkers. In this study, we identified SARS-CoV-2 infection as a high risk factor for sepsis. Our study may provide a potential therapeutic direction for the treatment of COVID-19 patients suffering from sepsis.