Recent studies have confirmed that different signaling pathways are involved in the pathogenesis of Alzheimer’s disease (AD), and that complex molecular connections exist between these pathways. Autophagy, or the natural degradation of the cell, is crucial for the breakdown and production of harmful proteins in AD, and it shows a number of links with other AD-related processes. Considering this central role of autophagy in AD, scientists from Shanghai Maritime University aimed to identify genes related to clinical outcomes that are connected to autophagy within and between the pathways in AD.
To uncover the feature messenger RNAs (single-stranded RNA molecules complementary to one of the DNA strands of a gene) involved in the crosstalk between autophagy and other AD-related pathways, researchers used the pathway analysis based on global impact (PAGI) method. Then, the weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of feature messenger RNAs and differential long non-coding RNAs (RNAs that regulate gene expression). Finally, scientists used multivariate Cox regression to build a prognosis model based on two autophagy-related crosstalk genes (CD40 and SMAD7), which could predict the overall survival of AD patients with medium-to-high accuracy.
This study developed an excellent strategy for extracting autophagy-related significant genes based on pathway crosstalk in AD, and biomarkers valuable to the prognosis of AD were discovered, which may also play an essential role in the development and treatment of AD.
最近的研究證實，阿爾茨海默病（Alzheimer’s disease，AD）的發病機制涉及不同的信號通路，並且這些通路之間存在著複雜的分子聯繫。自噬或細胞的自然降解對於 AD 中有害蛋白質的分解和產生至關重要，並且它顯示出與其他 AD 相關過程的許多聯繫。考慮到自噬在 AD 中的核心作用，上海海事大學的科學家旨在確定與 AD 通路內和通路之間的自噬相關的臨床結果相關基因。
為了揭示參與自噬和其他 AD 相關通路之間串擾的特徵信使 RNA（與基因的 DNA 鏈之一互補的單鏈 RNA 分子），研究人員使用了基於全局影響 (PAGI) 方法的通路分析。然後，使用加權基因共表達網絡分析（WGCNA）構建了特徵信使RNA和差異長非編碼RNA（調節基因表達的RNA）的共表達模塊。最後，科學家利用多變量 Cox 回歸構建了基於兩個自噬相關串擾基因（CD40 和 SMAD7）的預後模型，該模型可以中高準確度預測 AD 患者的總體生存率。
本研究開發了一種基於AD通路串擾提取自噬相關重要基因的優秀策略，並發現了對AD預後有價值的生物標誌物，這些標誌物也可能在AD的發生和治療中發揮重要作用。
Reference: Qian F, Kong W, Wang S. Exploring autophagy related prognostic genes of Alzheimer’s disease based on pathway crosstalk analysis. Bosn J of Basic Med Sci [Internet]. 2022Apr.2 [cited 2022Apr.17];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7019
Editor: Merima Bukva, MPharm
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