Anyomi Bright Kwaku, Fosu Kwadwo, Lamptey Emmanuel Lante, Agegnehu Solomon Baynesagne, Quarshie Jude Tetteh, Kampo Sylvanus, Wei Jianshe
Institute for Brain Sciences Research, School of Life Sciences, Henan University, Jinming Avenue, Kaifeng 475004, China.
West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), P.O. Box LG 77, University of Ghana, Accra 00233, Ghana.
ACS Omega. 2025 Apr 24;10(17):17651-17660. doi: 10.1021/acsomega.4c11571. eCollection 2025 May 6.
Alzheimer's disease (AD) has been largely prevalent among the older population. With the increasing incidence of cancer over the years, scientists have explored the relationship between these two conditions which were formerly associated with aging. Interestingly, an inverse relationship between cancer and AD has been observed in large cohort studies which has garnered substantial interest. While this inverse relationship presents a fascinating scientific puzzle, there is limited data on the molecular mechanisms that govern this phenomenon. This study aims to investigate the fundamental molecular mechanisms driving the inverse association between AD and three common cancers: breast, prostate, and colorectal cancers. Gene expression data for AD were obtained from the Gene Expression Omnibus (GEO) repository, specifically the GSE122063 data set. Differentially expressed genes (DEGs) between AD and nondemented controls were identified using the GEO2R tool. Genes associated with breast, prostate, and colorectal cancer were obtained from the Genecards database. Shared genes between cancers and AD-upregulated genes were identified using the Venny 2.1 tool. The UALCAN analysis portal was used to evaluate the mRNA expression of shared genes in cancer types. The DAVID tool, ShinyGO and SRplotter tools were used for functional enrichment analyses and gene ontology annotations. We found 20 genes upregulated in AD but significantly downregulated in breast cancer, 11 significantly downregulated in prostate cancer and 5 genes downregulated in colon cancer. Key genes were involved in pathways related to muscle structure, DNA repair, protein stability, and gene expression regulation. Three (3) of these genes, , , and , were downregulated in all three cancers and may play an important role in reduced risk of cancer development while upregulated in AD. This study serves as a foundational effort to delve deeper into the molecular connections between AD and various cancer types, using the identified genes as a promising starting point for future experimental investigations to fully elucidate the mechanisms involved in the inverse interaction and protection of AD patients against cancer development.
阿尔茨海默病（AD）在老年人群中极为普遍。随着多年来癌症发病率的上升，科学家们探索了这两种以前与衰老相关的疾病之间的关系。有趣的是，在大型队列研究中观察到癌症与AD之间存在负相关关系，这引起了广泛关注。虽然这种负相关关系提出了一个引人入胜的科学谜题，但关于控制这一现象的分子机制的数据却很有限。本研究旨在探讨驱动AD与三种常见癌症（乳腺癌、前列腺癌和结直肠癌）之间负相关关系的基本分子机制。AD的基因表达数据来自基因表达综合数据库（GEO），具体为GSE122063数据集。使用GEO2R工具鉴定AD与非痴呆对照之间的差异表达基因（DEG）。与乳腺癌、前列腺癌和结直肠癌相关的基因从Genecards数据库中获取。使用Venny 2.1工具鉴定癌症与AD上调基因之间的共享基因。UALCAN分析门户用于评估癌症类型中共享基因的mRNA表达。DAVID工具、ShinyGO和SRplotter工具用于功能富集分析和基因本体注释。我们发现20个基因在AD中上调但在乳腺癌中显著下调，11个在前列腺癌中显著下调，5个在结肠癌中下调。关键基因参与了与肌肉结构、DNA修复、蛋白质稳定性和基因表达调控相关的途径。其中三个基因， 、 和 ，在所有三种癌症中均下调，可能在降低癌症发生风险中起重要作用，而在AD中上调。本研究作为一项基础性工作，深入探讨了AD与各种癌症类型之间的分子联系，将鉴定出的基因作为未来实验研究的有希望的起点，以充分阐明AD患者与癌症发生之间负向相互作用和保护的机制。
