Chen Youfang, Zhou Feng, Lu Weicheng, Zeng Weian, Wang Xudong, Xie Jingdun
Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation for Cancer Medicine, Guangzhou, Guangdong, China.
Department of Neurology, First People's Hospital of Foshan, Foshan, Guangdong, China.
Front Psychiatry. 2022 Oct 21;13:1004945. doi: 10.3389/fpsyt.2022.1004945. eCollection 2022.
Major depressive disorder (MDD) is a heterogeneous and prevalent mental disorder associated with increased morbidity, disability, and mortality. However, its underlying mechanisms remain unclear.
All analyses were conducted based on integrated samples from the GEO database. Differential expression analysis, unsupervised consensus clustering analysis, enrichment analysis, and regulation network analysis were performed.
Mitogen-activated protein kinase (MAPK) signaling pathway was identified as an associated pathway in the development of MDD. From transcriptional signatures, we classified the MDD patients into two subgroups using unsupervised clustering and revealed 13 differential expression genes between subgroups, which indicates the probably relative complications. We further illustrated potential molecular mechanisms of MDD, including dysregulation in the neurotrophin signaling pathway, peptidyl-serine phosphorylation, and endocrine resistance. Moreover, we identified hub genes, including MAPK8, TP53, and HRAS in the maintenance of MDD. Furthermore, we demonstrated that the axis of miRNAs-TFs-HRAS/TP53/MAPK8 may play a critical role in MDD.
Taken together, we demonstrated an overview of MAPK-related key genes in MDD, determined two molecular subtypes, and identified the key genes and core network that may contribute to the procession of MDD.
重度抑郁症（MDD）是一种异质性且普遍存在的精神障碍，与发病率、残疾率和死亡率的增加相关。然而，其潜在机制仍不清楚。
所有分析均基于来自基因表达综合数据库（GEO数据库）的整合样本进行。进行了差异表达分析、无监督一致性聚类分析、富集分析和调控网络分析。
丝裂原活化蛋白激酶（MAPK）信号通路被确定为MDD发生发展中的一条相关通路。通过转录特征，我们使用无监督聚类将MDD患者分为两个亚组，并揭示了亚组间13个差异表达基因，这表明可能存在相对的并发症。我们进一步阐述了MDD的潜在分子机制，包括神经营养因子信号通路失调、肽基丝氨酸磷酸化和内分泌抵抗。此外，我们确定了维持MDD状态的关键基因，包括MAPK8、TP53和HRAS。此外，我们证明了miRNA-转录因子-HRAS/TP53/MAPK8轴可能在MDD中起关键作用。
综上所述，我们展示了MDD中与MAPK相关的关键基因概况，确定了两种分子亚型，并鉴定了可能导致MDD进展的关键基因和核心网络。
