Abstract
Alzheimer's disease (AD) and colorectal cancer (CRC) are two kind of age-related diseases with a negative correlation in risk of prevalence. In this study, we aimed to identify the hub genes and immune-associated biomarkers contributing to the inverse relationship between AD and CRC. The gene expression data from public repositories and the bioinformatics techniques, including differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms, were integrated to screen the hub genes that are inversely expressed in AD and CRC. The immunohistochemistry (IHC) analysis was performed to validate the identified hub genes in the cancer tissues from CRC patients or brain tissues from 5×FAD mice. We have identified 6 hub genes, including EBNA1BP2, PPA1, CCT4, SLC39A10, RAN, and PPA1, which potentially play critical roles in the negative correlation between AD and CRC and might provide valuable insights for the diagnosis, therapy, and prognosis of AD or CRC. Functional enrichment analysis highlighted the immune system's crucial roles in connecting AD and CRC processes. Moreover, the percent of immune cell infiltration in brain or colorectal tissues were different in patients with AD or CRC, offering insights for targeted immunotherapies. Finally, the expression of EBNA1BP2, PPA1 and SLC39A10 were validated to be downregulated in AD, but upregulated in CRC. In conclusion, these results suggested that some hub genes, such as EBNA1BP2, PPA1 and SLC39A10, might contribute to the inverse relationship between AD and CRC, which lay a foundation for further investigating the underlying mechanism, as well as for the development of novel diagnostic and therapeutic strategies for this two diseases.