scholarly journals PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3065
Author(s):  
Shreya Udawant ◽  
Carl Litif ◽  
Alma Lopez ◽  
Bonnie Gunn ◽  
Erin Schuenzel ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Enrichment Analysis ◽  
Pi3k Pathway ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
Clinical Samples ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Dual Inhibitor ◽  
The Impact

Glioblastoma (GBM) is the most lethal primary brain cancer that lacks effective molecular targeted therapies. The PI3K/AKT/mTOR pathway is activated in 90% of all Glioblastoma multiforme (GBM) tumors. To gain insight into the impact of the PI3K pathway on GBM metabolism, we treated U87MG GBM cells with NVP-BEZ235 (PI3K and mTOR a dual inhibitor) and identified differentially expressed genes with RNA-seq analysis. RNA-seq identified 7803 differentially regulated genes in response to NVP-BEZ235. Gene Set Enrichment Analysis (GSEA) identified two glycolysis-related gene sets that were significantly enriched (p < 0.05) in control samples compared to NVP-BEZ235-treated samples. We validated the inhibition of glycolytic genes by NVP-BEZ235 and examined the impact of the FOXO1 inhibitor (AS1842856) on these genes in a set of GBM cell lines. FOXO1 inhibition alone was associated with reduced LDHA expression, but not ENO1 or PKM2. Bioinformatics analyses revealed that PI3K-impacted glycolytic genes were over-expressed and co-expressed in GBM clinical samples. The elevated expression of PI3K-impacted glycolytic genes was associated with poor prognosis in GBM based on Kaplan–Meier survival analyses. Our results suggest novel insights into hallmark metabolic reprogramming associated with the PI3K-mTOR dual inhibition.

scholarly journals Dysregulation of ribosome-related genes in ankylosing spondylitis: a systems biology approach and experimental method

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Arezou Lari ◽  
Hamid Gholami Pourbadie ◽  
Ali Sharifi-Zarchi ◽  
Maryam Akhtari ◽  
Leila Nejatbakhsh Samimi ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Ribosome Biogenesis ◽  
Enrichment Analysis ◽  
Microarray Dataset ◽  
Gene Set Enrichment Analysis ◽  
Rna Seq ◽  
Gene Set Enrichment ◽  
Bioinformatics Analyses ◽  
Autoimmune Rheumatic Disease ◽  
Gene Associations

Abstract Background Ankylosing spondylitis (AS) is an autoimmune rheumatic disease. Few candidate gene associations have been reported for AS and the current understanding of its pathogenesis remains still poor. Thus, the exact mechanism of AS is needed to urgently be disclosed. The purpose of this study was to identify candidate genes involving in AS disease. Methods and results GSE25101 publicly available microarray and GSE117769 RNA-seq datasets of AS patients were obtained for bioinformatics analyses. Gene set enrichment analysis showed that in the microarray dataset, the ribosome pathway was significantly up-regulated in AS compared with controls. Furthermore, some ribosomal components demonstrated overexpression in patients in the RNA-seq dataset. To confirm the findings, 20 AS patients and 20 matching controls were selected from the Rheumatology Research Center clinic, Shariati Hospital. PBMCs were separated from whole blood and RNA contents were extracted. Following the results of datasets analysis, the expression level of rRNA5.8S pseudogene, rRNA18S pseudogene, RPL23, RPL7, and RPL17 genes were measured through real-time PCR. Our findings showed dysregulation of rRNA5.8S and rRNA18S pseudogenes, and also the RPL17 gene in patients. Conclusion Considering that genes involved in ribosome biogenesis contributed to some AS-associated biological processes as well as diseases that have comorbidities with AS, our results might advance our understanding of the pathological mechanisms of ankylosing spondylitis.

scholarly journals Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Enrichment Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Cytolytic Activity ◽  
Gene Set Enrichment Analysis ◽  
Preoperative Treatment ◽  
Rna Seq

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

scholarly journals In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Zhipeng Zhu ◽  
Jiuhua Xu ◽  
Xiaofang Wu ◽  
Sihao Lin ◽  
Lulu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

scholarly journals Bioinformatics-based Screening of Key Genes for Saponin Metabolism in Quinoa

2021 ◽  
Author(s):  
Chengang Guo ◽  
Zhimin wei ◽  
Wei Lyu ◽  
Yanlou Geng
Keyword(s):  
Differentially Expressed Genes ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Hierarchical Cluster ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Differential Analysis ◽  
Rna Seq ◽  
Protein Coding ◽  
Key Genes

Abstract Quinoa saponins have complex, diverse and evident physiologic activities. However, the key regulatory genes for quinoa saponin metabolism are not yet well studied. The purpose of this study was to explore genes closely related to quinoa saponin metabolism. In this study, the significantly differentially expressed genes in yellow quinoa were firstly screened based on RNA-seq technology. Then, the key genes for saponin metabolism were selected by gene set enrichment analysis (GSEA) and principal component analysis (PCA) statistical methods. Finally, the specificity of the key genes was verified by hierarchical clustering. The results of differential analysis showed that 1654 differentially expressed genes were achieved after pseudogenes deletion. Therein, there were 142 long non-coding genes and 1512 protein-coding genes. Based on GSEA analysis, 116 key candidate genes were found to be significantly correlated with quinoa saponin metabolism. Through PCA dimension reduction analysis, 57 key genes were finally obtained. Hierarchical cluster analysis further demonstrated that these key genes can clearly separate the four groups of samples. The present results could provide references for the breeding of sweet quinoa and would be helpful for the rational utilization of quinoa saponins.

scholarly journals Identification of RRM2 as a Potential Biomarker for the Diagnosis and Prognosis of Rheumatoid Arthritis

2021 ◽  
Author(s):  
Wu Biao ◽  
Yufeng Chen ◽  
Junlong Zhong ◽  
Shuping Zhong ◽  
Bin Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Clinical Samples ◽  
Healthy Controls ◽  
Rna Seq ◽  
Hub Genes ◽  
Healthy Human ◽  
Bioinformatics Analyses ◽  
Potential Biomarker

Abstract Background: Rheumatoid arthritis (RA) is a common autoimmune disease that can occur at any age. If treatment is delayed, RA can seriously affect the patients’ quality of life. However, there is no diagnostic criteria for RA and the positive predictive value of the current biomarkers is moderate. Objective: to identify RA-associated susceptibility genes and explore their potential as a novel biomarker for diagnosis and evaluation of the prognosis of RA.Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy human donors and RA patients. RNA-seq analyses were performed to identify the differentially expressed genes (DEGs) between RA and control samples. The PBMCs-mRNA in DEGs were further subjected to enrichment analysis. Furthermore, the hub genes and key modules associated with RA were screened by bioinformatics analyses. Then, the expression of hub genes in RA were assessed in mRNA expression profiles. Next, real time-quantitative PCR (RT-qPCR) analyses were performed to further confirm the expression of the hub genes from the PBMCs that collected from 47 patients with RA and 40 healthy controls. Finally, we evaluated the clinical characters for the candidate mRNAs.Results: RNA-seq analyses revealed the expression of 178 mRNAs from PBMCs were disregulated between the healthy controls and the RA patients. Bioinformatics analyses revealed 10 hub mRNAs. The top 3 significant functional modules screened from PPI network functionally were involved in DNA replication origin binding, chemokine activity, etc. After validating the 10 hub mRNAs in GSE93272 dataset and clinical samples, we identified 3 candidate mRNAs, including ASPM, DTL and RRM2. Among which, RRM2 showed great capacity in discriminating between remissive RA and active RA. Significant correlations were observed between DTL and IL-8, TNF-α, between RRM2 and CDAI, DAS-28, tender joints and swollen joints, respectively. The AUC values of ASPM, DTL and RRM2 were 0.654, 0.995 and 0.990, respectively.Conclusion: We successfully identified multiple candidate mRNAs associated with RA. RRM2 showed high diagnosis efficiency with the AUC of 0.990 (sensitivity=100%, specificity=97.5%). And RRM2 severed as an additional biomarker for evaluating disease activity. The findings provided a novel candidate biomarker for diagnosis and evaluation of the prognosis of RA.

scholarly journals Identification of Core Genes and Screening of Potential Targets in Glioblastoma Multiforme by Integrated Bioinformatic Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Ji’an Yang ◽  
Qian Yang
Keyword(s):  
Glioblastoma Multiforme ◽  
Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Hypergeometric Test ◽  
Ppi Network ◽  
Neuropsychiatric Diseases ◽  
Core Genes

Glioblastoma multiforme is the most common primary intracranial malignancy, but its etiology and pathogenesis are still unclear. With the deepening of human genome research, the research of glioma subtype screening based on core molecules has become more in-depth. In the present study, we screened out differentially expressed genes (DEGs) through reanalyzing the glioblastoma multiforme (GBM) datasets GSE90598 from the Gene Expression Omnibus (GEO), the GBM dataset TCGA-GBM and the low-grade glioma (LGG) dataset TCGA-LGG from the Cancer Genome Atlas (TCGA). A total of 150 intersecting DEGs were found, of which 48 were upregulated and 102 were downregulated. These DEGs from GSE90598 dataset were enriched using the overrepresentation method, and multiple enriched gene ontology (GO) function terms were significantly correlated with neural cell signal transduction. DEGs between GBM and LGG were analyzed by gene set enrichment analysis (GSEA), and the significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in synapse signaling and oxytocin signaling pathways. Then, a protein-protein interaction (PPI) network was constructed to assess the interaction of proteins encoded by the DEGs. MCODE identified 2 modules from the PPI network. The 11 genes with the highest degrees in module 1 were designated as core molecules, namely, GABRD, KCNC1, KCNA1, SYT1, CACNG3, OPALIN, CD163, HPCAL4, ANK3, KIF5A, and MS4A6A, which were mainly enriched in ionic signaling-related pathways. Survival analysis of the GSE83300 dataset verified the significant relationship between expression levels of the 11 core genes and survival. Finally, the core molecules of GBM and the DrugBank database were assessed by a hypergeometric test to identify 10 drugs included tetrachlorodecaoxide related to cancer and neuropsychiatric diseases. Further studies are required to explore these core genes for their potentiality in diagnosis, prognosis, and targeted therapy and explain the relationship among ionic signaling-related pathways, neuropsychiatric diseases and neurological tumors.

scholarly journals Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Shen ◽  
Li-rong Xu ◽  
Xiao Tang ◽  
Chang-po Lin ◽  
Dong Yan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Plasma Cells ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gamma Delta ◽  
Hub Genes ◽  
Gene Set Enrichment ◽  
Bioinformatics Analyses ◽  
Immune Infiltration ◽  
Atheromatous Plaques

Abstract Background Atherosclerosis is a chronic inflammatory disease that affects multiple arteries. Numerous studies have shown the inherent immune diversity in atheromatous plaques and suggest that the dysfunction of different immune cells plays an important role in atherosclerosis. However, few comprehensive bioinformatics analyses have investigated the potential coordinators that might orchestrate different immune cells to exacerbate atherosclerosis. Methods Immune infiltration of 69 atheromatous plaques from different arterial beds in GSE100927 were explored by single-sample-gene-set enrichment analysis (presented as ssGSEA scores), ESTIMATE algorithm (presented as immune scores) and CIBERSORT algorithm (presented as relative fractions of 22 types of immune cells) to divide these plaques into ImmuneScoreL cluster (of low immune infiltration) and ImmuneScoreH cluster (of high immune infiltration). Subsequently, comprehensive bioinformatics analyses including differentially-expressed-genes (DEGs) analysis, protein–protein interaction networks analysis, hub genes analysis, Gene-Ontology-terms and KEGG pathway enrichment analysis, gene set enrichment analysis, analysis of expression profiles of immune-related genes, correlation analysis between DEGs and hub genes and immune cells were conducted. GSE28829 was analysed to cross-validate the results in GSE100927. Results Immune-related pathways, including interferon-related pathways and PD-1 signalling, were highly enriched in the ImmuneScoreH cluster. HLA-related (except for HLA-DRB6) and immune checkpoint genes (IDO1, PDCD-1, CD274(PD-L1), CD47), RORC, IFNGR1, STAT1 and JAK2 were upregulated in the ImmuneScoreH cluster, whereas FTO, CRY1, RORB, and PER1 were downregulated. Atheromatous plaques in the ImmuneScoreH cluster had higher proportions of M0 macrophages and gamma delta T cells but lower proportions of plasma cells and monocytes (p < 0.05). CAPG, CECR1, IL18, IGSF6, FBP1, HLA-DPA1 and MMP7 were commonly related to these immune cells. In addition, the advanced-stage carotid plaques in GSE28829 exhibited higher immune infiltration than early-stage carotid plaques. Conclusions Atheromatous plaques with higher immune scores were likely at a more clinically advanced stage. The progression of atherosclerosis might be related to CAPG, IGSF6, IL18, CECR1, FBP1, MMP7, FTO, CRY1, RORB, RORC, PER1, HLA-DPA1 and immune-related pathways (IFN-γ pathway and PD-1 signalling pathway). These genes and pathways might play important roles in regulating immune cells such as M0 macrophages, gamma delta T cells, plasma cells and monocytes and might serve as potential therapeutic targets for atherosclerosis.

The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation

2021 ◽  
Author(s):  
Shan Yang ◽  
Wei Gao ◽  
Haoqi Wang ◽  
Xi Zhang ◽  
Yunzhe Mi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Clinical Samples

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

scholarly journals Transcriptomic Prediction of Pig Liver-Enriched Gene 1 Functions in a Liver Cell Line

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 412
Author(s):  
Zhe Zhang ◽  
Zizengchen Wang ◽  
Yanna Dang ◽  
Jinyang Wang ◽  
Sakthidasan Jayaprakash ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Liver Cells ◽  
Cellular Level ◽  
Gene Set Enrichment Analysis ◽  
Functional Study ◽  
Rna Seq ◽  
Gene Set Enrichment ◽  
Functional Studies ◽  
Er Stress Response ◽  
Domain Of Unknown Function

The newly identified liver-enriched gene 1 (LEG1) encodes a protein with a characteristic domain of unknown function 781 (DUF781/LEG1), constituting a protein family with only one member in mammals. A functional study in zebrafish suggested that LEG1 genes are involved in liver development, while the platypus LEG1 homolog, Monotreme Lactation Protein (MLP), which is enriched in the mammary gland and milk, acts as an antibacterial substance. However, no functional studies on eutherian LEG1s have been published to date. Thus, we here report the first functional prediction study at the cellular level. As previously reported, eutherian LEG1s can be classified into three paralogous groups. Pigs have all three LEG1 genes (pLEG1s), while humans and mice have retained only LEG1a. Hence, pLEG1s might represent an ideal model for studying LEG1 gene functions. RNA-seq was performed by the overexpression of pLEG1s and platypus MLP in HepG2 cells. Enrichment analysis showed that pLEG1a and pLEG1b might exhibit little function in liver cells; however, pLEG1c is probably involved in the endoplasmic reticulum (ER) stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus MLP shows antibacterial activity, confirming the functional study in platypus. Therefore, our study showed from the transcriptomic perspective that mammalian LEG1s have different functions in liver cells due to the subfunctionalization of paralogous genes.

scholarly journals Sex-specific Transcriptomic Differences From Human Dorsal Root Ganglia Associated With Painful Radiculopathy

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Robert Y North ◽  
Yan Li ◽  
Pradipta Ray ◽  
Laurence D Rhines ◽  
Claudio E Tatsui ◽  
...  
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Epidemiological Studies ◽  
Gene Set Enrichment Analysis ◽  
Afferent Neurons ◽  
Rna Seq ◽  
Cord Injury ◽  
Medical Histories

Abstract INTRODUCTION Women are at greater risk to suffer from many chronic pain conditions, more often report painful symptoms in epidemiological studies, and demonstrate greater pain sensitivity to experimentally measured pain responses. There is growing evidence from animal models for sex-specific biological differences in nociception, particularly involving primary afferent neurons, that may contribute to these differences. However, the details and extent of sex-specific differences associated with pain in human afferent neurons has not been previously investigated. METHODS Human dorsal root ganglia (DRG) and medical histories were obtained from patients undergoing spinal surgery that necessitated sacrifice of spinal nerve roots as part of standard of care. Clinical data for presence of painful radiculopathy was obtained through retrospective review of medical records or collected at study enrollment. RNA sequencing (RNA-seq) was performed on 21 DRG from 15 patients with variable presence of radicular pain reported in a corresponding dermatome. Differential expression analysis for male w/pain (MP) vs female w/pain (FP) samples was performed with thresholds for robustly expressed autosomal genes (TPM >3.0), fold change of 2.0 or higher, with false discovery rate (FDR) <0.05. RESULTS Comparison of the MP and FP cohorts yielded 575 differentially expressed genes with 426 upregulated in MP and 149 upregulated in FP. Gene set enrichment analysis demonstrated significant differences in genes related to inflammation and immune regulation (increased MAPK and BDNF signaling in MP, increased Rhodopsin-like GPCR in FP) and differing clusters of spinal cord injury-associated genes (TLR4, AIF1, OMG, C1QB increased in FP, EGR1, NR4A1, ZFP36, BTG2, MYC in MP). CONCLUSION Utilizing RNA-seq of human DRG innervating regions of pain, this study provides the first demonstration of sex-specific differences for the biology of pain within the dorsal root ganglion in humans and implicates the immune system as a critical influence in these differences.

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