Correlation and diagnostic significance of serum LncRNA NEAT1 and SP1 with H-Y grade in patients with Parkinson's disease
-
摘要:
目的 探讨帕金森病(PD)患者血清中长链非编码RNA核旁斑组装转录本1(LncRNA NEAT1)和特异性蛋白1(SP1)的表达水平与疾病严重程度的关系。 方法 选取2020年11月—2022年1月东莞市滨海湾中心医院收治的80例PD患者(PD组),根据修订版Hoehn-Yahr(H-Y)分级分为轻度PD亚组26例、中度PD亚组31例、重度PD亚组23例,选取同期57名体检健康者作为对照组。比较各组血清LncRNA NEAT1、SP1 mRNA表达差异及与H-Y分级的相关性,采用ROC曲线分析两者表达对PD的诊断价值。 结果 PD组血清LncRNA NEAT1、SP1 mRNA表达高于对照组(t=6.887、6.303,P<0.001)。轻度、中度、重度PD亚组血清LncRNA NEAT1、SP1 mRNA表达依次升高(F=66.803、H=59.259,P<0.001)。PD患者血清LncRNA NEAT1、SP1 mRNA表达与H-Y分级呈正相关关系(rs=0.790、0.840,P<0.001),两者单独与联合诊断PD的曲线下面积分别为0.787、0.784、0.858,灵敏度分别为58.75%、51.25%、70.00%,特异度分别为91.23%、96.49%、89.47%。 结论 PD患者血清LncRNA NEAT1、SP1 mRNA表达升高与病情进展密切相关,LncRNA NEAT1、SP1的表达水平对PD具有一定的诊断价值,且联合诊断价值更高。 -
关键词:
- 帕金森病 /
- 长链非编码RNA核旁斑组装转录本1 /
- 特异性蛋白1 /
- 诊断
Abstract:Objective To investigate the expression levels of long non-coding RNA para-plaque assembly transcript 1 (LncRNA NEAT1) and SP1 in the serum of patients with Parkinson's disease (PD) and their relationship with disease severity. Methods A total of 80 patients with PD (PD group) admitted to Binhaiwan Central Hospital of Dongguan from November 2020 to January 2022 were selected and divided into mild PD subgroup (n=26), moderate PD subgroup (n=31) and severe PD subgroup (n=23) according to the revised Hoehn-Yahr (H-Y) classification, and 57 healthy subjects (control group) were selected during the same period. The differences in serum LncRNA NEAT1, and SP1 mRNA expression in each group and their correlation with the H-Y stage were compared. The ROC curve was used to analyze the diagnostic value of the expression of lncRNA NEAT1 and SP1 in PD. Results The serum levels of LncRNA NEAT1 and SP1 mRNA in the PD group were higher than those in the control group (t=6.887, 6.303, all P < 0.001). The serum levels of LncRNA NEAT1 and SP1 mRNA in mild, moderate, and severe PD subgroups increased in turn (F=66.803, H=59.259, all P < 0.001). The expressions of serum LncRNA NEAT1 and SP1 mRNA in PD patients were positively correlated with the H-Y stage (rs=0.790, 0.840, P < 0.001), and the areas under the curve were 0.787, 0.784, and 0.858, respectively. The sensitivity was 58.75%, 51.25% and 70.00%, and the specificity was 91.23%, 96.49% and 89.47%, respectively. Conclusion The increased expression of serum LncRNA NEAT1 and SP1 mRNA in PD patients is closely related to the progression of the disease, which has a certain diagnostic value for PD, and the combined diagnostic value is higher. -
表 1 2组血清LncRNA NEAT1、SP1 mRNA表达比较(x±s)
Table 1. Comparison of serum LncRNA NEAT1 and SP1 mRNA expression between the two groups(x±s)
组别 例数 LncRNA NEAT1 SP1 mRNA 对照组 57 1.14±0.17 0.97±0.16 PD组 80 1.39±0.25 1.17±0.20 t值 6.887 6.303 P值 <0.001 <0.001 表 2 不同病情程度PD患者血清LncRNA NEAT1、SP1 mRNA表达比较
Table 2. Comparison of serum LncRNA NEAT1 and SP1 mRNA expression in PD patients with different disease levels
组别 例数 LncRNA NEAT1(x±s) SP1 mRNA[M(P25, P75)] 轻度PD亚组 26 1.18±0.17 0.97(0.90, 1.07) 中度PD亚组 31 1.35±0.16a 1.19(1.11, 1.24)a 重度PD亚组 23 1.69±0.13ab 1.36(1.32, 1.48)ab 统计量 66.803c 59.259d P值 <0.001 <0.001 注:与轻度PD亚组比较,aP<0.05;与中度PD亚组比较,bP<0.05。c为F值,d为H值。 表 3 血清LncRNA NEAT1、SP1 mRNA表达单独与联合诊断PD的价值
Table 3. Value of serum LncRNA NEAT1and SP1 expression in diagnosis of PD alone and in combination
指标 曲线下面积及95% CI 最佳截断值 灵敏度(%) 特异度(%) Youden指数 LncRNA NEAT1 0.787(0.708~0.852) 1.35 58.75 91.23 0.500 SP1 mRNA 0.784(0.705~0.849) 1.17 51.25 96.49 0.477 二者联合 0.858(0.788~0.912) 70.00 89.47 0.595 -
[1] TOLOSA E, GARRIDO A, SCHOLZ S W, et al. Challenges in the diagnosis of Parkinson's disease[J]. Lancet Neurol, 2021, 20(5): 385-397. doi: 10.1016/S1474-4422(21)00030-2 [2] HAYES M T. Parkinson's disease and Parkinsonism[J]. Am J Med, 2019, 132(7): 802-807. doi: 10.1016/j.amjmed.2019.03.001 [3] 中华医学会神经病学分会帕金森病及运动障碍学组, 中国医师协会神经内科医师分会帕金森病及运动障碍学组. 早发型帕金森病的诊断与治疗中国专家共识[J]. 中华神经医学杂志, 2021, 20(2): 109-116. doi: 10.3760/cma.j.cn115354-20201119-00903Parkinson's Disease and movement Disorders Group, Chinese Medical Association Neurology Branch, and Parkinson's Disease and movement Disorders Group, Chinese Medical Doctor Association Neurology Branch. Chinese expert consensus on diagnoses and treatments of early-onset Parkinson's disease[J]. Chinese Journal of Neuromedicine, 2021, 20(2): 109-116. doi: 10.3760/cma.j.cn115354-20201119-00903 [4] 曹津津, 宋琼, 邹春林. 细胞治疗帕金森病的研究进展[J]. 天津医药, 2022, 50(4): 428-433. https://www.cnki.com.cn/Article/CJFDTOTAL-TJYZ202204017.htmCAO J J, SONG Q, ZHOU C L. Recent advances in cell therapy for Parkinson's disease[J]. Tianjin Medical Journal, 2022, 50(4): 428-433. https://www.cnki.com.cn/Article/CJFDTOTAL-TJYZ202204017.htm [5] SALEMI M, LANZA G, MOGAVERO M P, et al. A transcriptome analysis of mRNAs and long non-coding RNAs in patients with Parkinson's disease[J]. Int J Mol Sci, 2022, 23(3): 1535. doi: 10.3390/ijms23031535 [6] LIU Y, LU Z. Long non-coding RNA NEAT1 mediates the toxic of Parkinson's disease induced by MPTP/MPP+ via regulation of gene expression[J]. Clin Exp Pharmacol Physiol, 2018, 45(8): 841-848. doi: 10.1111/1440-1681.12932 [7] WU Z, DU Y, LI Z, et al. Soldier caste-specific protein 1 is involved in soldier differentiation in termite reticulitermes aculabialis[J]. Insects, 2022, 13(6): 502. doi: 10.3390/insects13060502 [8] YAO L, DAI X, SUN Y, et al. Inhibition of transcription factor SP1 produces neuroprotective effects through decreasing MAO B activity in MPTP/MPP+ Parkinson's disease models[J]. J Neurosci Res, 2018, 96(10): 1663-1676. doi: 10.1002/jnr.24266 [9] HOEHN M M, YAHR M D. Parkinsonism: onset, progression and mortality[J]. Neurology, 1967, 17(5): 427-442. doi: 10.1212/WNL.17.5.427 [10] QI S, YIN P, WANG L, et al. Prevalence of Parkinson's disease: a community-based study in China[J]. Mov Disord, 2021, 36(12): 2940-2944. doi: 10.1002/mds.28762 [11] SONG Z, LIU S, LI X, et al. Prevalence of Parkinson's disease in adults aged 65 years and older in China: a multicenter population-based survey[J]. Neuroepidemiology, 2022, 56(1): 50-58. doi: 10.1159/000520726 [12] 王伟, 曹庆华, 孙光玲, 等. 脑白质病变与帕金森病患者运动症状及非运动症状的相关性分析[J]. 中华全科医学, 2022, 20(2): 237-239. doi: 10.16766/j.cnki.issn.1674-4152.002321WANG W, CAO Q H, SUN G L, et al. Correlation analysis of white matter lesions and motor symptoms and non-motor symptoms in Parkinson's patients[J]. Chinese Journal of General Practice, 2022, 20(2): 237-239. doi: 10.16766/j.cnki.issn.1674-4152.002321 [13] LI Y, GU Z, LIN S, et al. Histone deacetylases as epigenetic targets for treating Parkinson's disease[J]. Brain Sci, 2022, 12(5): 672. doi: 10.3390/brainsci12050672 [14] TAGHIZADEH E, GHEIBIHAYAT S M, TAHERI F, et al. LncRNAs as putative biomarkers and therapeutic targets for Parkinson's disease[J]. Neurol Sci, 2021, 42(10): 4007-4015. doi: 10.1007/s10072-021-05408-7 [15] 欧诒丹, 高元杰, 陈静. GAS5靶向miR-128调控帕金森病模型细胞凋亡的分子机制[J]. 中国老年学杂志, 2022, 42(5): 1178-1182. doi: 10.3969/j.issn.1005-9202.2022.05.044OU Y D, GAO Y J, CHEN J. Molecular mechanism of GAS5 targeting miR-128 in regulating apoptosis of Parkinson's disease model cells[J]. Chinese Journal of Gerontology, 2022, 42(5): 1178-1182. doi: 10.3969/j.issn.1005-9202.2022.05.044 [16] CHEN C, ZHANG S, WEI Y, et al. LncRNA RMST regulates neuronal apoptosis and inflammatory response via sponging miR-150-5p in Parkinson's disease[J]. Neuroimmunomodulation, 2022, 29(1): 55-62. doi: 10.1159/000518212 [17] 张信远, 李德珠, 林瑶, 等. lncRNA NEAT1在中枢神经系统疾病中的研究进展[J]. 生物化学与生物物理进展, 2020, 47(11): 1174-1182. https://www.cnki.com.cn/Article/CJFDTOTAL-SHSW202011006.htmZHANG X Y, LI D Z, LIN Y, et al. Research Progress of Long lncRNA NEAT1in The Central Nervous System Diseases[J]. Progress in Biochemistry and Biophysics, 2020, 47(11): 1174-1182. https://www.cnki.com.cn/Article/CJFDTOTAL-SHSW202011006.htm [18] KE S, YANG Z, YANG F, et al. Long noncoding RNA NEAT1 aggravates Aβ-induced neuronal damage by targeting miR-107 in Alzheimer's disease[J]. Yonsei Med J, 2019, 60(7): 640-650. doi: 10.3349/ymj.2019.60.7.640 [19] JIN F, OU W, WEI B, et al. Transcriptome-wide analysis to identify the inflammatory role of lncRNA NEAT1 in experimental ischemic stroke[J]. J Inflamm Res, 2021, 14: 2667-2680. doi: 10.2147/JIR.S315281 [20] MARTÍNEZ-MENÁRGUEZ J Á, MARTÍNEZ-ALONSO E, CARA-ESTEBAN M, et al. Focus on the small GTPase Rab1: a key player in the pathogenesis of Parkinson's disease[J]. Int J Mol Sci, 2021, 22(21): 12087. doi: 10.3390/ijms222112087 [21] ZHOU S, ZHANG D, GUO J, et al. Deficiency of NEAT1 prevented MPP+-induced inflammatory response, oxidative stress and apoptosis in dopaminergic SK-N-SH neuroblastoma cells via miR-1277-5p/ARHGAP26 axis[J]. Brain Res, 2021, 1750: 147156. DOI: 10.1016/j.brainres.2020.147156. [22] GONZALEZ-HUNT C P, SANDERS L H. DNA damage and repair in Parkinson's disease: recent advances and new opportunities[J]. J Neurosci Res, 2021, 99(1): 180-189. doi: 10.1002/jnr.24592 [23] WANG D, CHEN F, FANG B, et al. MiR-128-3p alleviates spinal cord ischemia/reperfusion injury associated neuroinflammation and cellular apoptosis via SP1 suppression in rat[J]. Front Neurosci, 2020, 14: 609613. DOI: 10.3389/fnins.2020.609613. [24] DABROWSKA K, SKOWROŃSKA K, POPEK M, et al. The role of Nrf2 transcription factor and SP1-Nrf2 protein complex in glutamine transporter SN1 regulation in mouse cortical astrocytes exposed to ammonia[J]. Int J Mol Sci, 2021, 22(20): 11233. DOI: 10.3390/ijms222011233. [25] CAO Y, TAN X, LU Q, et al. miR-590-3 and SP1 promote neuronal apoptosis in patients with Alzheimer's disease via AMPK signaling pathway[J]. Contrast Media Mol Imaging, 2021, 2021: 6010362. DOI: 10.1155/2021/6010362. [26] SISWANTO F M, OGURO A, IMAOKA S. SP1 is a substrate of Keap1 and regulates the activity of CRL4AWDR23 ubiquitin ligase toward Nrf2[J]. J Biol Chem, 2021, 296: 100704. DOI: 10.1016/j.jbc.2021.100704. [27] CAI L J, TU L, LI T, et al. Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1[J]. Aging (Albany NY), 2020, 12(1): 672-689. [28] WANG S, WEN Q, XIONG B, et al. Long noncoding RNA NEAT1 knockdown ameliorates 1-Methyl-4-Phenylpyridine-Induced cell injury through microRNA-519a-3p/SP1 axis in Parkinson disease[J]. World Neurosurg, 2021, 156: e93-e103. doi: 10.1016/j.wneu.2021.08.147 -
下载: