Table_2_Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction.xlsx

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.

术后认知功能障碍（Postoperative Cognitive Dysfunction，POCD）是老年患者麻醉后常见的严重中枢神经系统功能紊乱。尽管其临床症状已得到充分认知，但POCD的分子病因学仍未阐明。截至目前，临床上既缺乏POCD的金标准分子诊断方法，也无有效的治疗手段。
因此，本研究旨在通过探究与POCD人类患者相关的长链非编码RNA（long non-coding RNA，lncRNAs）和信使RNA（messenger RNA，mRNAs），并解析其潜在调控通路，以阐明该疾病的分子机制。
本研究共招募200名需接受髋关节或膝关节置换术的患者，分别于术前1天及术后30天对其神经功能进行评估。同时，收集受试者的血清样本，采用微阵列分析技术对比POCD患者与非POCD患者的lncRNAs及mRNAs差异表达谱。
为进一步探究差异表达的mRNA与lncRNAs的作用机制，本研究对mRNA开展了基因本体（Gene Ontology，GO）功能富集分析、通路富集分析，并构建了lncRNA-mRNA互作网络。
结果显示，与非POCD组相比，POCD组中共存在68个异常表达的lncRNAs及115个异常表达的mRNAs。其中，本研究选取排名前十的上调lncRNAs与下调lncRNAs进行富集分析。
有趣的是，我们发现这些lncRNAs与mRNAs参与了多种生物学过程、分子功能及细胞组分，同时还涉及多条信号通路，这表明POCD的发病机制与lncRNAs和mRNAs的差异表达密切相关。
综上，非POCD患者与POCD患者之间的基因表达失调参与了POCD的发生与发展，有望作为POCD诊断的生物标志物以及治疗的药物靶点。