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血清 lncRNA ITGB2-AS1 和 ICAM-1 作为类风湿关节炎和骨关节炎诊断的新型生物标志物。

Serum lncRNA ITGB2-AS1 and ICAM-1 as novel biomarkers for rheumatoid arthritis and osteoarthritis diagnosis.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Cairo University, 23 Kasr El-Ainy Street, Cairo, 11562, Egypt.

Department of Rheumatology and Clinical Immunology, Internal Medicine, Kasr Al-Ainy, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

BMC Med Genomics. 2024 Oct 8;17(1):247. doi: 10.1186/s12920-024-01993-6.

Abstract

BACKGROUND

The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients.

SUBJECTS

Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included.

RESULTS

Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients.

CONCLUSION

Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.

摘要

背景

类风湿关节炎(RA)和骨关节炎(OA)的完整循环长非编码 RNA(lncRNA)特征仍未被揭示。整合素亚基β 2(ITGB2)反义 RNA 1(ITGB2-AS1)可影响 ITGB2 的表达;然而,关于其在 RA 和 OA 中的表达及其与配体细胞间黏附分子-1(ICAM-1)的临床用途的知识还存在空白。本研究旨在探讨血清 ITGB2-AS1 作为一种新型诊断生物标志物的潜力及其与 ITGB2 表达的相关性,以及与 RA 和原发性膝骨关节炎患者的疾病活动度和严重程度的相关性。

受试者

43 例 RA 患者、35 例膝骨关节炎患者和 22 名健康志愿者被纳入研究。

结果

与健康对照组相比,RA 患者血清 ITGB2-AS1 表达上调,但膝骨关节炎患者血清 ITGB2-AS1 表达无明显变化,而两种疾病患者血清 ICAM-1 蛋白水平均升高。在 RA 与对照组的受试者工作特征分析中,ITGB2-AS1 具有鉴别诊断 RA 的潜力(AUC=0.772),而 ICAM-1 则在 RA 和膝骨关节炎与对照组的比较中具有诊断潜力(AUC=0.804,0.914)。在多变量分析中,血清 ITGB2-AS1 和 ICAM-1 与发生 RA 的风险相关,而只有 ICAM-1 与发生膝骨关节炎的风险相关。联合 ITGB2-AS1 和 ICAM-1 的联合检测在 RA 中具有很好的诊断效能(AUC=0.9,敏感性=86.05%,特异性=91.67%)。有趣的是,RA 患者血清 ITGB2-AS1 与疾病活动度(DAS28)呈正相关,与两种疾病的 ITGB2mRNA 表达呈正相关,而 ICAM-1 与膝骨关节炎患者的 ITGB2 表达呈正相关。

结论

本研究表明,血清 ITGB2-AS1 是 RA 的一种新型潜在诊断生物标志物,与疾病活动度相关。联合检测 ITGB2-AS1 和 ICAM-1 的预测性联合检测可能在 RA 诊断中具有临床应用价值。我们还强调了 ICAM-1 与膝骨关节炎诊断的关系。血清 ITGB2-AS1 与两种疾病的 ITGB2 表达相关,这可能为进一步的机制研究提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee6a/11462822/32e9ff6c0d18/12920_2024_1993_Fig1_HTML.jpg

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