PLOS Genetics: Molecular Evidence for the Inverse Comorbidity between Central Nervous System Disorders and Cancers Detected by Transcriptomic Meta-analyses

There is epidemiological evidence that patients with certain Central
Nervous System (CNS) disorders have a lower than expected probability of
developing some types of Cancer. We tested here the hypothesis that
this inverse comorbidity is driven by molecular processes
common to CNS disorders and Cancers, and that are deregulated in
opposite directions. We conducted transcriptomic meta-analyses of three
CNS disorders (Alzheimer's disease, Parkinson's disease and
Schizophrenia) and three Cancer types (Lung, Prostate, Colorectal)
previously described with inverse comorbidities. A significant
overlap was observed between the genes upregulated in CNS disorders and
downregulated in Cancers, as well as between the genes downregulated in
CNS disorders and upregulated in Cancers. We also observed expression
deregulations in opposite directions at the level of pathways. Our
analysis points to specific genes and pathways, the upregulation of
which could increase the incidence of CNS disorders and simultaneously
lower the risk of developing Cancer, while the downregulation of another
set of genes and pathways could contribute to a decrease in the
incidence of CNS disorders while increasing the Cancer risk. These
results reinforce the previously proposed involvement of the PIN1 gene, Wnt and P53 pathways, and reveal potential new candidates, in particular related with protein degradation processes.

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