Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis

Abstract

Background. Long noncoding RNAs (lncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific lncRNAs and mRNAs and their related networks in knee osteoarthritis (KOA). Methods. The dataset GSE98918, which included 24 meniscus samples and related clinical data, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed lncRNAs and mRNAs, we constructed the coexpression network using WGCNA (weighted correlation network analysis) and identified the critical module related to KOA. For mRNAs in the key module, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using the DAVID database. A competing endogenous RNA network (ceRNA) based on the screened mRNAs, lncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub lncRNAs and mRNAs were screened, and the diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. Hub mRNAs were validated using the dataset GSE113825. Results. We screened 208 significantly differentially expressed lncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Coexpression network based on the enriched differentially expressed lncRNAs and mRNAs in the green module uncovered 5 lncRNAs and 56 mRNAs. The lncRNA-miRNA-mRNA ceRNA network revealed that lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, lnc-RTN2-1, IGFBP4 (insulin-like growth factor binding protein 4), and KLF2 (Kruppel-like factor 2) were significantly correlated with the meniscus degeneration of KOA. ROC curve analysis revealed that these hub lncRNAs and mRNAs showed excellent diagnostic value for KOA. Conclusions. These hub lncRNAs and mRNAs were potential prognostic biomarkers for the meniscus degeneration of KOA. Further studies are required to validate these new biomarkers and better understand the pathological process of the meniscus degeneration of KOA.

Identification of Novel Key Genes and Pathways in Multiple Sclerosis Based on Weighted Gene Coexpression Network Analysis and Long Noncoding RNA-Associated Competing Endogenous RNA Network

“…Considering that lncRNAs are involved in MS development, as observed in recent studies, we further constructed an lncRNA-associated ceRNA network in the key module only. This analytical process has been proved to be effective in identifying pivotal lncRNAs, and the ceRNA network constructed is beneficial for exploring the regulatory mechanism in multiple disorders, such as hepatocellular carcinoma and knee osteoarthritis [20,21]. We also identified hub genes and evaluated their usefulness for the prognosis of MS.…”

Identification of key biomarkers in steroid-induced osteonecrosis of the femoral head and their correlation with immune infiltration by bioinformatics analysis

“…According to the annotation information of the GPL15207 and GPL1355 platform, the data probes were transformed to gene symbols. Then, the associated package of R (version 4.0.2) was performed to preprocess these data, including background correction, add the missing values, and quantile normalization [ 14 ].…”

Integrated Analysis of lncRNA and mRNA Expression Profiles Indicates Age-Related Changes in Meniscus

“…The expressions of 208 lncRNAs and mRNAs were significantly differential between patients with knee osteoarthritis and non-knee osteoarthritis group. In the knee osteoarthritis group, a total of five lncRNAs were significantly associated with meniscus degeneration ( Zhao et al, 2020a ). However, until now, the role of lncRNAs in age-related change of meniscus is poorly known.…”