Given 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.

We 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).

The 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%.

The 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.

鉴于 lncRNA 在人类疾病中所起的作用以及 OA 的高发病率，本研究调查了与该疾病相关的关键途径，并确定了 OA 诊断的潜在生物标志物。

我们首先对来自 6 名受试者（3 名 OA 和 3 名健康对照）的外周血白细胞中的 RNA 测序进行了探索。有希望的候选 lncRNA 在第一阶段验证中使用 38 名受试者（20 名 OA 和 18 名健康对照）的 GEO 数据集（GSE114007）进行评估，然后使用定量 PCR 分析对 101 名受试者（67 名 OA 和 34 名对照）进行第二阶段验证。第三阶段调查了经验证的 lncRNA 在外周血白细胞中 OA 早期诊断中的潜在价值，共有 120 名参与者（60 名病例和 60 名对照）。

该数据集共识别出 1,380 个上调和 719 个下调的 mRNA，以及 5,743 个上调和 7,384 个下调的 lncRNA。上调的DEGs主要富集在细胞外基质中，而下调的DEGs主要富集在IL-17和wnt信号通路中。18 个重叠的候选 lncRNA 在第一阶段验证后存活。选择 3 个 hub lncRNA 进行第二阶段验证，并在外部样本中合格，lncRNALINC00167进一步证实了类似的结果（在两个阶段均下调）。接收者操作特征分析表明，LINC00167可以将 OA 病例与健康对照区分开来，曲线下面积高，为 0.879 (95%CI: 0.819, 0.938;磷< 0.001)，灵敏度为 80.7%，特异性为 83.5%。

OA 的表达谱已被确定，关键通路通过从易于获取的血液中进行 RNA-seq 的综合方法来阐明。LINC00167在临床实践中可作为 OA 的潜在早期诊断标志物。这种lncRNA的详细作用机制需要在未来的研究中进一步阐明。