RNA Sequencing Reveals LINC00167 as a Potential Diagnosis Biomarker for Primary Osteoarthritis: A Multi-Stage Study.

Liying Jiang,Minjie Chu,Qirong Qian,Ziyuan Ma,Yi Chen,Xun Zhuang,Yuhui Yu,Yiqin Zhou,Shengli Xia,Junjie Shen

doi:10.3389/fgene.2020.539489

Abstract

ObjectivesGiven the roles played by lncRNA in human diseases and the high incidence of OA, this study investigated the pivotal pathways involved in the disease and identified potential biomarkers for OA diagnosis.MethodsWe first performed an exploration of RNA-sequencing in peripheral blood leukocytes from six subjects (3 OA and 3 healthy controls). Promising candidate lncRNAs were evaluated in first stage validation using a GEO dataset (GSE114007) of 38 subjects (20 OA and 18 healthy controls), followed by a second stage validation using quantitative PCR analysis with 101 subjects (67 OA and 34 controls). The third stage investigated the potential value of validated lncRNA in the early diagnosis of OA in peripheral blood leukocytes from a total of 120 participants (60 cases and 60 controls).ResultsThe dataset identified a total of 1,380 up-regulated and 719 down-regulated mRNAs and 5,743 up-regulated and 7,384 down-regulated lncRNAs. The up-regulated DEGs were mainly enriched in the extracellular matrix, while the down-regulated DEGs were mainly enriched in the IL-17 and wnt signaling pathways. 18 overlapping candidate lncRNAs survived after first-stage validation. 3 hub lncRNAs were selected for the second validation stage and qualified in an external sample, and lncRNA LINC00167 was further confirmed with a similar result (down-expressed in both stages). Receiver operating characteristic analysis showed that LINC00167 can distinguish OA cases from healthy controls with a high area under the curve of 0.879 (95%CI: 0.819, 0.938; P < 0.001), with a sensitivity of 80.7% and specificity of 83.5%.ConclusionThe expression profile of OA was identified and critical pathways were elucidated by an integrated approach to RNA-seq from easily accessible blood. LINC00167 may serve as a potential early diagnosis marker for OA in clinical practice. The detailed mechanism of action of this lncRNA requires further elucidation in future studies.

Highlights

Osteoarthritis (OA) is a common and disabling condition characterized by articular cartilage degradation
In a study by Fu et al (2015) there were 3,007 upregulated Long non-coding RNAs (lncRNAs) and 1,707 down-regulated lncRNAs in knee OA cartilage compared to normal samples and some of them were predicted to have target genes that were associated with OA
Numerous research has shown that lncRNAs play a critical role in the regulation of chondrocyte and synovial cell survival (Dou et al, 2017; Zheng et al, 2017; Cao et al, 2018), as well as in mediating inflammation (Pearson and Jones, 2016) and angiogenesis (Cen et al, 2017)

Summary

Introduction

Osteoarthritis (OA) is a common and disabling condition characterized by articular cartilage degradation. It creates substantial and increasing burdens for healthcare with notable implications for elderly individuals (Hermann et al, 2018; Piwowar et al, 2018). Several studies have shown that lncRNAs play important roles in malignancy and chronic diseases, including OA (Peffers et al, 2018; Razmara et al, 2019; Wu et al, 2019). A recent study reported that NON-HSAG034351 was the hub lncRNA down-regulated in synovial tissue and could play a central role in the pathological progression of OA (Shui et al, 2020)

Objectives

Methods

Results

Conclusion