环状 RNA 表达谱在系统性红斑狼疮中的表现及其作为一种潜在新型生物标志物的临床意义。
Circular RNA expression profile of systemic lupus erythematosus and its clinical significance as a potential novel biomarker.
机构信息
Department of Dermatology/Venerology, the First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China.
Department of Rheumatology, the First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China.
出版信息
Genes Genomics. 2022 Nov;44(11):1405-1414. doi: 10.1007/s13258-022-01315-z. Epub 2022 Sep 27.
BACKGROUND
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are more abundant, specific, and highly organized than linear RNAs. Increasing evidence supports that circRNAs may serve as diagnostic biomarkers in many diseases, but their potential as biomarkers in systemic lupus erythematosus (SLE) remains unclear.
OBJECTIVE
We investigated the critical circRNAs involved in SLE progression and explored their potential application as biomarkers in SLE.
METHOD
RNA sequencing was conducted on peripheral blood mononuclear cells (PBMCs) from 4 SLE patients and 4 healthy volunteers. CircRNA profile data were analyzed to identify differentially expressed circRNAs and visualized via R software. After screening, qPCR analysis of target circRNA expression was performed using PBMCs from 31 SLE patients and 35 healthy volunteers. Correlations between circRNA expression levels and the SLEDAI score were assessed via Spearman correlation analysis. Finally, the performance of circRNAs as biomarkers in SLE was examined by receiver operating characteristic curve analysis.
RESULTS
The result identified six differentially expressed circRNAs between SLE patients and healthy controls: hsa_circ_0006689, hsa_circ_0070562, hsa_circ_0006117, hsa_circ_0007683, hsa_circ_0042519, and hsa_circ_0008647. The validation analysis showed differing relative expression levels of hsa_circ_0007683, hsa_circ_0042519, hsa_circ_0008647, and hsa_circ_0006689 between SLE patients and healthy volunteers (P < 0.05), and hsa_circ_0006689 expression in PBMCs correlated with the SLEDAI score (P < 0.05). Furthermore, addition of hsa_circ_0006689 expression increased the sensitivities of anti-dsDNA antibody and anti-Sm antibody levels for SLE diagnosis (from 29.03 to 61.30% and 32.26-71.00%, respectively).
CONCLUSION
Our results suggest hsa_circ_0006689 may be a useful circRNA biomarker for SLE diagnosis and prognosis.
背景
环状 RNA（circRNA）是一类内源性非编码 RNA，其丰度、特异性和组织性均优于线性 RNA。越来越多的证据表明，circRNA 可能作为许多疾病的诊断生物标志物，但它们在系统性红斑狼疮（SLE）中的潜在应用仍不清楚。
目的
我们研究了参与 SLE 进展的关键 circRNA，并探讨了它们作为 SLE 生物标志物的潜在应用。
方法
对 4 例 SLE 患者和 4 例健康志愿者的外周血单个核细胞（PBMC）进行 RNA 测序。使用 R 软件分析 circRNA 谱数据，以识别差异表达的 circRNA 并进行可视化。筛选后，使用 31 例 SLE 患者和 35 例健康志愿者的 PBMC 进行目标 circRNA 表达的 qPCR 分析。通过 Spearman 相关性分析评估 circRNA 表达水平与 SLEDAI 评分之间的相关性。最后，通过接收者操作特征曲线分析检查 circRNA 作为 SLE 生物标志物的性能。
结果
该研究确定了 SLE 患者与健康对照组之间的 6 个差异表达 circRNA：hsa_circ_0006689、hsa_circ_0070562、hsa_circ_0006117、hsa_circ_0007683、hsa_circ_0042519 和 hsa_circ_0008647。验证分析显示，hsa_circ_0007683、hsa_circ_0042519、hsa_circ_0008647 和 hsa_circ_0006689 在 SLE 患者和健康志愿者之间的相对表达水平存在差异（P<0.05），并且 hsa_circ_0006689 在 PBMC 中的表达与 SLEDAI 评分相关（P<0.05）。此外，hsa_circ_0006689 表达的增加提高了抗 dsDNA 抗体和抗 Sm 抗体水平诊断 SLE 的敏感性（分别从 29.03%增加到 61.30%和从 32.26%增加到 71.00%）。
结论
我们的研究结果表明，hsa_circ_0006689 可能是 SLE 诊断和预后的有用 circRNA 生物标志物。
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