Expression data from human patients with slow or rapid Parkinson's Disease progression

Parkinson’s Disease is a multi-system, disabling progressive neurodegenerative condition. Clinical progression is highly heterogeneous and, thus far, there are not available biomarkers to accurately predict the rate of disease progression. Thus, identifying molecular signatures that allow discriminating between different progression rates might significantly assist the therapeutic strategy, and enable improved outcomes in clinical trials. We performed an exploratory cross-sectional study aimed at determining whether gene expression differences in peripheral blood may be used to discriminate between patients with slow or rapid Parkinson’s disease progression Based on distinct disease stages and rates of motor disease progression, 70 Parkinson's Disease patients were clinically evaluated and divided into the two groups: slow (n=35) or rapid (n=35) progression. RNA was extracted from whole blood samples of these patients. RNA quality was assessed using RIN in the two groups of patients, which displayed mean RIN values of 7.14 (rapid progressors) and 7.02 (slow progressors). From the 70 RNA samples, 3 had RIN<6 and were not included in subsequent analysis (this corresponded to 1 rapid and 2 slow progressors samples). Expression analysis included 67 array samples (34 rapid and 33 slow progressors).. Gene expression profiling was performed using RNA expression data generated by genome array plates (Affymetrix Human Genome U219 platform, HG-U219). Patients Classification: Patients Classification: Patients were consecutively recruited from the movement disorders outpatient clinic of the Lisbon University Hospital. Neurologists with expertise in movement disorders interviewed and examined all cases. Patients were divided into two distinct groups with “Slow” or “Fast” progression, depending on the absence or presence of postural instability, respectively. Postural instability was defined by item 3.12 of the MDS-UPDRS, part III. Slow progression if scored 0 (no postural instability) and rapid progression if scored ≥ 1. Sample Collection: Venous blood from Parkinson's Disease patients was collected in PAXgene tubes

帕金森病（Parkinson’s Disease）是一种多系统受累的致残性进行性神经退行性疾病。其临床进展具有高度异质性，目前尚无可用的生物标志物可精准预测疾病进展速率。因此，识别能够区分不同进展速率的分子特征，有望显著助力治疗策略的制定，并改善临床试验的结局。本研究开展了一项探索性横断面研究，旨在探讨外周血基因表达差异是否可用于区分进展缓慢或快速的帕金森病患者。研究基于不同疾病分期与运动症状进展速率，对70名帕金森病患者进行临床评估，并将其分为两组：进展缓慢组（n=35）与进展快速组（n=35）。研究人员提取了上述患者全血样本中的RNA。采用RNA完整性数（RIN, RNA Integrity Number）评估两组患者的RNA质量，两组的平均RIN值分别为7.14（快速进展组）与7.02（缓慢进展组）。70份RNA样本中，有3份RIN<6，未纳入后续分析（其中1份来自快速进展组，2份来自缓慢进展组）。最终纳入表达分析的样本共67份，其中快速进展组34份，缓慢进展组33份。基因表达谱分析采用基于基因组阵列板（Affymetrix人类基因组U219平台，HG-U219）生成的RNA表达数据完成。患者分组：研究对象连续招募自里斯本大学医院运动障碍门诊。由具备运动障碍疾病诊疗专长的神经科医师对所有病例进行访谈与检查。根据是否存在姿势不稳将患者分为两个独立组别：缓慢进展组与快速进展组。姿势不稳的判定依据运动障碍协会统一帕金森病评定量表第三部分（MDS-UPDRS）的第3.12项：评分为0（无姿势不稳）者归为缓慢进展组，评分≥1者归为快速进展组。样本采集：帕金森病患者的静脉血采集于PAXgene采血管中。