COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration

Li, Shushan; Wang, Haitao; Zhang, Yi; Qiao, Renqiu; Xia, Peige; Kong, Zhiheng; Zhao, Hongbo; Yin, Li

doi:10.3389/fgene.2021.721258

Cited by 31 publications

(25 citation statements)

References 36 publications

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“…In this study, we detected those macrophages and most other immune cells were highly infiltrated in the OA synovium. Previous histology-based studies have also demonstrated macrophage enrichment in OA ( 28 , 29 ). Due to their essential roles in immune recruitment, inflammatory damage, and ECM degradation, macrophages have received much attention and are thought to be important lesion driver immune cells in OAs.…”

Section: Discussionmentioning

confidence: 77%

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Liu

Han

et al. 2022

Front. Immunol.

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BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.

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Section: Discussionmentioning

confidence: 77%

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Liu

Han

et al. 2022

Front. Immunol.

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“…These results implied that silencing of COL3A1 suppressed malignant behaviors of TNBC. On the other hand, COL3A1 upregulation has been validated to facilitate immune evasion in cancers (Fang et al, 2021; Li et al, 2021). In this study, we observed the suppressive effect of COL3A1 knockdown on immune evasion in MDA‐MB‐231 and BT‐549 cells, as evidenced by increased LDH release and the percentage of CD8 + T cells along with reduced apoptosis rate of CD8 + T cells and the protein level of PD‐L1.…”

Section: Discussionmentioning

confidence: 99%

Silencing of COL3A1 represses proliferation, migration, invasion, and immune escape of triple negative breast cancer cells via down‐regulating PD‐L1 expression

Yang

et al. 2022

Cell Biology International

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This study is designed to illuminate the specific role and underlying mechanism of collagen type III alpha 1 chain (COL3A1) in triple negative breast cancer (TNBC).Quantitative real-time polymerase chain reaction was applied to examine mRNA expression of COL3A1. Western blot analysis was employed to determine protein levels of COL3A1, programmed death ligand 1 (PD-L1), Bcl-2, and cleaved caspase-3. Immunohistochemistry staining was utilized for assessing protein expression of Ki67 and COL3A1 in tissues. The proliferous capacity of cells was assessed through CCK-8 assay and 5-Ethynyl-2′-deoxyuridine assay. Cell apoptosis and the percentage of CD8 + T cells were measured using flow cytometry. Migration and invasion of TNBC cells were examined via transwell assay. Lactate dehydrogenase (LDH) release was measured via a LDH assay kit. For establishing a xenograft tumor model, MDA-MB-231 cells were injected into the flank of mice through subcutaneous injection. COL3A1 expression was raised in TNBC tissues and cells, and it was inversely associated with overall survival data of TNBC patients. COL3A1 downregulation repressed proliferation, invasion, migration, and immune escape of TNBC cells along with tumor growth of xenograft mice. In TNBC cells and tumor tissues of mice, protein expression of PD-L1 was reduced by COL3A1 knockdown. COL3A1 knockdown-mediated inhibitory effects on cell proliferation, migration, invasion, and immune escape were reversed by PD-L1 upregulation in vitro. Silencing of COL3A1 exerted an antitumor role in TNBC, implying its potential as a therapeutic target for TNBC.

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“…Module C was also critical, and six upregulated genes including COL5A2, COL5A1, COL3A1, COL1A1, COL1A2, and PCOLCE were found in Module C. A previous study indicated that COL5A1 was involved in the OA synovium elevation of collagens and cross-linking enzymes ( Tsezou, 2014 ). One previous study showed that COL3A1 may be a potential diagnostic biomarker for OA ( Li et al, 2021 ). Another study demonstrated that the expression levels of COL1A1 and COL5A1 were significantly upregulated in OA ( Zhu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Microarray Data Identify Hub Genes Involved in Osteoarthritis

Zhou

Zou²,

Wan

et al. 2022

Front. Genet.

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The present study was performed to explore the underlying molecular mechanisms and screen hub genes of osteoarthritis (OA) via bioinformatics analysis. In total, twenty-five OA synovial tissue samples and 25 normal synovial tissue samples were derived from three datasets, namely, GSE55457, GSE55235, and GSE1919, and were used to identify the differentially expressed genes (DEGs) of OA by R language. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A Venn diagram was built to show the potential hub genes identified in all three datasets. The STRING database was used for constructing the protein–protein interaction (PPI) networks and submodules of DEGs. We identified 507 upregulated and 620 downregulated genes. Upregulated DEGs were significantly involved in immune response, MHC class II receptor activity, and presented in the extracellular region, while downregulated DEGs were mainly enriched in response to organic substances, extracellular region parts, and cadmium ion binding. Results of KEGG analysis indicated that the upregulated DEGs mainly existed in cell adhesion molecules (CAMs), while downregulated DEGs were significantly involved in the MAPK signaling pathway. A total of eighteen intersection genes were identified across the three datasets. These include Nell-1, ATF3, RhoB, STC1, and VEGFA. In addition, 10 hub genes including CXCL12, CXCL8, CCL20, and CCL4 were found in the PPI network and module construction. Identification of DEGs and hub genes associated with OA may be helpful for revealing the molecular mechanisms of OA and further promotes the development of relevant biomarkers and drug targets.

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COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration

Cited by 31 publications

References 36 publications

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

Silencing of COL3A1 represses proliferation, migration, invasion, and immune escape of triple negative breast cancer cells via down‐regulating PD‐L1 expression

Gene Expression Microarray Data Identify Hub Genes Involved in Osteoarthritis

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