Transcriptome signatures reveal candidate key genes in the whole blood of patients with lumbar disc prolapse
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA511447 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The present study aimed to investigate differentially expressed genes in whole blood obtained from patients with lumbar disc prolapse and healthy volunteers. A total of 8 patients with lumbar disc prolapse and 8 healthy volunteers were recruited. An Agilent SurePrint G3 human gene expression microarray 8x60 K was used to perform the microarray analyses.
2019-12-03 | GSE124272 | GEO
Project description:The present study aimed to investigate differentially expressed genes (DEGs) in whole blood (WB) obtained from patients with lumbar disc prolapse (LDP) and healthy volunteers. A total of 8 patients with LDP and 8 healthy volunteers were recruited. An Agilent SurePrint G3 human gene expression microarray 8×60 K was used to perform the microarray analyses. R was employed to identify DEGs, which were then subjected to bioinformatics analysis, including a Gene Ontology (GO) analysis, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis. DEGs in the degenerative annulus fibrosis (AF) and nucleus pulposus (NP) compared with non-degenerative tissues were also identified based on microarray data and the intersections of the three were assessed. Furthermore, reverse transcription-quantitative (RT-q)PCR was performed to confirm the aberrant expression levels of selected DEGs in the WB of all subjects. A total of 161 DEGs between LDP patients and the healthy controls were identified (128 upregulated and 33 downregulated). These DEGs were enriched in 293 biological process, 36 cellular component and 21 molecular function GO terms, as well as in 24 KEGG pathways. The PPI network contained 4 submodules, and Toll-like receptor 4 had the highest degree centrality. A total of 22 DEGs were common to the three groups of DEGs. The RT-qPCR assay confirmed that the expression levels of cytochrome P450 family 27 subfamily A member 1, superoxide dismutase 2, protein disulfide isomerase family A member 4, FKBP prolyl isomerase 11 and ectonucleotide pyrophosphatase/phosphodiesterase 4 were significantly different between the patient group and the volunteer group. In conclusion, several genes were identified as potential biomarkers in WB that should be further explored in future studies to determine their potential application in the clinical treatment and diagnosis of LDP, and the present bioinformatics analysis revealed several GO terms, KEGG pathways and submodules of the PPI network that may be involved in LDP, although the exact mechanisms remain elusive.
| S-EPMC6862187 | biostudies-literature
Project description:Lumbar intervertebral disc mRNA sequencing identifies the regulatory pathway in patients with disc herniation and spondylolisthesis
| PRJNA612336 | ENA
Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily physical activity, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. The proteome reflects the long-term accumulation of proteins and their turnover with time, which cannot be faithfully determined by the transcriptome that reflects only immediate cellular changes. The proteome of the disc, which is predominantly extracellular matrix, may therefore more accurately reflect disc function, and could provide important information about the niche in which disc cells are embedded in and can also impact on cellular function. Unfortunately, the acquisition of young healthy IVD tissues from surgeries are scarce, and it is exceedingly rare to obtain healthy samples with spatial information. Here, we examined three young healthy cadaveric lumbar discs, corresponding to three neighboring levels (L3/4, L4/5 and L5/S1), from one individual (16M); and analysed the proteome profiles of the NP, inner AF (IAF) and outer AF (OAF), in a direction-specific (both lateral and anteroposterior) manner, to gain a reference proteome of healthy discs. We identified that the central-most regions of the disc (including NP and IAF) are similar to each other and there is expression of well characterized NP markers (including KRT8/19, CD109), as well as upregulation of cartilage and cytoskeletal-related proteins (including CHRD, CHRDL2, FRZB). Furthermore, in the PCA plot, there is clear demarcation of inner and outer AF, which was found to express small proteoglycans (BGN, DCN, FMOD, OGN, PRELP) and a unique group of the collagens (COL12A1, COL14A1, COL1A1, COL6A1/2/3) and glycoproteins including CILP, CILP2, COMP, FBN1and THBS1. We also showed that in young disc, the upper levels are more similar to each other than the lower disc levels, and that directional factors (whether the tissue was from an anteroposterior or lateral direction) play minimal roles, although we also identified four modules showing strong directional trends. Using the young proteome as a baseline reference, we then examined three aged cadaveric lumbar discs (with same disc levels as the young) from another older individual (59M) to gain further understanding of age-related changes in the disc. Employing ANOVA, PCA and DEG analyses, the aged inner disc regions (including NP and IAF) were found to have similar profiles, express fewer classical NP markers, and have reduced numbers of differentially expressed proteins (DEPs) in comparison to young disc. Overall, both inner compartments and OAF of the aged disc showed an enrichment of proteins associated with inflammation and degradation. Remarkably, we discovered that in aged disc, the IAF and OAF distinction remains strong, and that the upper lumbar disc was deviated more away from their young counterparts than the lower two levels, with minimal influence by directional differences. Importantly, we further identified an abundance of blood proteins that were highly expressed in inner disc of aged discs, which suggested that age-related changes may have originated from the central NP regions of the disc. We carried out additional validation studies by examining the transcriptome of 2 independent young and aged samples, respectively, and were able to correlate transcriptome to young and aged proteome. Unique and novel to this study, we also correlated MRI imaging of the 3 aged lumbar discs and showed that there is correlation of particular types of proteins with MRI image intensity. In all, this data shed lights on the proteomic changes underlying the ageing IVDs in a region-specific manner.
2021-01-29 | PXD017740 | Pride
Project description:Here, we show results from next generation RNA sequencing (RNA-seq) on mRNA isolated from 10 human nucleus pulposus (NP) samples of lumbar degenerated discs (DH and DS; n=5 for each tissue) and other musculoskeletal tissues (Bone, cartilage, growth plate, and muscle; n=7 for each tissue). Pathway and network analyses based on gene ontology (GO) terms were used to identify the biological functions of differentially expressed mRNAs. A total of 701 genes were found to be significantly upregulated in lumbar NP tissue compared to other musculoskeletal tissues. These differentially expressed mRNAs were primarily involved in DNA damage, immunity and G1/S transition of mitotic cell cycle. Interestingly, DH-specific signaling genes showed major network in chemotactic (e.g., CXCL10, CXCL11, IL1RL2 and IL6) and matrix-degrading pathway (e.g., MMP16, ADAMTSL1, 5, 8, 12, and 15), while DS-specific signaling genes were found to be those involved in cell adhesion (e.g., CDH1, EPHA1and EFNA2) and inflammatory cytokines (e.g., CD19, CXCL5, CCL24, 25 and XCL2). Our findings provide new leads for therapeutic drug discovery that would permit optimization of medical or pharmacological intervention for cases of lumbar DDD.
2020-07-01 | GSE146904 | GEO
Project description:Given the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socio-economic challenge to the aging population, which is importantly attributed to intervertebral disc degeneration (IVDD), a highly prevalent affliction of aging. Elastic nucleus pulposus (NP) tissue is essential for maintenance of IVD structural and functional integrity. Native NP cells exhibit crucial functions for regulating extracellular matrix homeostasis, constructing an accommodating biomechanical environment and maintaining the gelatinous property of NP tissue. Mechanical stresses, including compulsion position and aberrant mechanical loading, are regarded as etiological factors of IVDD, and to further investigate the effect of mechanical exercise during the degeneration of IVDs, we surgically resected the lumbar 4th-lumbar 5th (L4-L5) spinous processes of the rat spine along with the supraspinous and interspinous ligaments to induce lumbar surgical instability (LSI). Additionally, we applied RNA sequencing technology to describe the degeneration-associated molecular atlas of the LSI model during exercise, and found that exercise accelerated the degenerative process of IVDs from LSI, which is involved in cytosolic DNA sensing-mediated inflammatory activation, similar to the degenerative patterns of the clinical IVDD process.
2024-07-17 | GSE266883 | GEO
Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.
2018-12-10 | PXD011467 | Pride
Project description:Asporin, also known as periodontal ligament-associated protein 1 (PLAP1), is a member of the family of small leucine-rich proteoglycan (SLRP) family. It is present within the cartilage extracellular matrix (ECM), and is reported have a genetic association with osteoarthritis. Its D14 allele has recently been found to be associated with lumbar disc degeneration in Asian subjects. There have been no studies, however, of this gene’s normal immunohistochemical localization within the human intervertebral disc, nor of expression levels in Caucasian individuals with disc degeneration. Studies were approved by our human subjects Institutional Review Board. Methods included immunohistochemical localization of asporin in the disc of humans and the sand rat (a small rodent with spontaneous age-related disc degeneration), and Affymetrix microarray analysis of asporin gene expression in vivo and in vitro. mmunohistochemical studies of human discs revealed that some, but not all, cells of the outer annulus expressed asporin. Fewer cells in the inner annulus contained asporin, and it was rarely present in cells in the nucleus pulposus. Similar patterns were found for the presence of asporin in lumbar discs of sand rats. Substantial relative gene expression levels were seen for asporin in both disc tissue and in annulus cells grown in three-dimensional culture. More degenerate human discs (Thompson grade 4) showed higher expression levels of asporin than did less degenerate (grade 1, 2 and 3) discs, p = 0.004. In the discs of Caucasian subjects studied here, and in the sand rat, greater immunolocalization levels were found in the outer compared to inner annulus. Localization was rare in the nucleus. Gene expression studies showed greatest expression of asporin in the more degenerate human discs in vivo.
2009-03-24 | GSE15227 | GEO
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.
2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress
Project description:Asporin, also known as periodontal ligament-associated protein 1 (PLAP1), is a member of the family of small leucine-rich proteoglycan (SLRP) family. It is present within the cartilage extracellular matrix (ECM), and is reported have a genetic association with osteoarthritis. Its D14 allele has recently been found to be associated with lumbar disc degeneration in Asian subjects. There have been no studies, however, of this gene’s normal immunohistochemical localization within the human intervertebral disc, nor of expression levels in Caucasian individuals with disc degeneration. Studies were approved by our human subjects Institutional Review Board. Methods included immunohistochemical localization of asporin in the disc of humans and the sand rat (a small rodent with spontaneous age-related disc degeneration), and Affymetrix microarray analysis of asporin gene expression in vivo and in vitro. mmunohistochemical studies of human discs revealed that some, but not all, cells of the outer annulus expressed asporin. Fewer cells in the inner annulus contained asporin, and it was rarely present in cells in the nucleus pulposus. Similar patterns were found for the presence of asporin in lumbar discs of sand rats. Substantial relative gene expression levels were seen for asporin in both disc tissue and in annulus cells grown in three-dimensional culture. More degenerate human discs (Thompson grade 4) showed higher expression levels of asporin than did less degenerate (grade 1, 2 and 3) discs, p = 0.004. In the discs of Caucasian subjects studied here, and in the sand rat, greater immunolocalization levels were found in the outer compared to inner annulus. Localization was rare in the nucleus. Gene expression studies showed greatest expression of asporin in the more degenerate human discs in vivo. Disc Tissue samples were obtained via the National Cancer Institute Cooperative Tissue Network (CHTN) as well as surgical disc procedures performed on patients with herniated discs and degenerative disc disease. Tissue was fixed and paraffin embedded. Standard laser capture microdissection (LCM) techniques were used to collect the cells from which total RNA was isolated and analyzed via microarray. Based on the Thompson scouring system, unhealthy discs (grade 4) were compared to healthy discs (grades 2,3).
2009-03-24 | E-GEOD-15227 | biostudies-arrayexpress