Identification of the molecular mechanism and diagnostic biomarkers in the thoracic ossification of the ligamentum flavum using metabolomics and transcriptomics

Li, Jiahao; Yu, Lingjia; Guo, Shigong; Zhao, Yu

doi:10.21203/rs.3.rs-16887/v2

Cited by 1 publication

(1 citation statement)

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“…To date, genetic, stress, ageing, in ammatory and metabolic factors have been found to be associated with the TOLF, whose etiological heterogeneity may indicate distinctive pathological phenotypes. [5][6][7][8][9] Except for susceptible middle-aged and elderly people, anecdotal observations indicated that a clinical subset of younger patients with obesity also suffered from severe or even diffuse TOLF. Additionally, concrete evidence has identi ed obesity as an independent causal factor for the development of TOLF in nonelderly adults.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Expression Profiling and Functional Signatures of Individualized Obesity-Associated Genes in Ossification of Ligamentum Flavum Through RNA-Sequence Data Mining

Zhang

Yuan

Chen

et al. 2021

Preprint

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Background: Obese individuals predispose to ossification of ligamentum flavum (OLF), whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood, especially during early life. This study aimed to explore obesity-associated genes and their functional signatures in OLF. Methods: Gene microarray expression data related to OLF were downloaded from the GSE106253 dataset in the Gene Expression Omnibus (GEO) database. The potential obesity-related differentially expressed genes (ORDEGs) in OLF were screened. Then, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI) were used to identify hub ORDEGs, and Metascape was used to further verify the key signaling pathways and immune-related function signatures of hub ORDEGs. Finally, correlation analysis of hub ORDEGs and identified OLF-related infiltrating immune cells (OIICs) was constructed to understand the possible mechanical link among obesity, immune response and OLF. Results: OLF-related differentially expressed genes and 2051 obesity-related genes from four databases were intersected to obtain 99 ORDEGs, including 54 upregulated and 55 downregulated genes. GO and KEGG analysis revealed that these genes were mainly involved in metabolism, inflammation and immune-related biological functions and pathways. A PPI network was established to determine 14 hub genes (AKT1, CCL2, CCL5, CXCL2, ICAM1, IL10, MYC, PTGS2, SAA1, SOCS1, SOCS3, STAT3, TNFRSF1B and VEGFA). The co-expression network demonstrated that this module was associated with cellular response to biotic stimulus, regulation of inflammatory response, regulation of tyrosine phosphorylation of STAT protein. Furthermore, Metascape functional annotations showed that hub genes were mainly involved in receptor signaling pathway via JAK-STAT, response to TNF and regulation of defense response, and their representative enriched pathways were TNF, adipocytokine and JAK-STAT signaling pathways. Subgroup analysis indicated that T cell activation might be potential immune function processes involved, and correlation analysis revealed that cDCs, memory B-cells and preadipocytes were highly correlated infiltrating immune cells. Conclusions: Our study deciphered individualized obesity-associated gene signature for the first time, which may facilitate exploring the underlying cellular and molecular pathogenesis and novel therapeutic targets of obesity-related early-onset OLF.

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Section: Introductionmentioning

confidence: 99%