Abstract:
Epidemiological studies and clinical evidence suggest an inverse comorbidity between cancer and
Alzheimer’s Disease (AD). Several epidemiological studies and biological evidence suggested
liver cancer (HCC) and Oesophageal cancer (EC) as most related to AD. Gene expression studies
conducted on microarray platforms have also reported genes and biological pathways as inversely
regulated between both diseases. However, to best of our knowledge no study has reported
molecular level association between AD and EC. Therefore, this study conducts meta-differential
expression analysis to get DEGs and pathways inversely regulated between cancer (Oesophageal
cancer, Liver cancer) and Alzheimer disease. Two RNA-seq datasets from AD patients and
controls from similar brain regions and four datasets from two different cancer types were
subjected to differential expression analysis. Meta-analysis was performed using p-value
combination method implicated in metaRNASeq. Intersection for inverse genes in each pair was
calculated and significance of overlap was tested through Fisher exact test. Inversely regulated
genes were then subjected to pathway analysis. Both cancer types (EC, LC) showed a significant
overlap in gene expression deregulation in the opposite direction from AD. Functional enrichment
comparison revealed several biological pathways which were affected jointly in both diseases,
including PI3K/AKT/MTOR, GABAergic, Central Carbon Metabolism in Cancer and Metabolic
pathways. Sixteen pathways were found to be deregulated in opposite direction. These results
reinforce the previously proposed gene candidates and pathways like PI3K/AKT/MTOR and
GABAergic synapse as contributing factor towards true inverse association between cancers and
AD. It also reveals new potential candidates and pathways that can be involved.
