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Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by

Kristina Ibáñez1, César Boullosa1, Rafael Tabarés-Seisdedos2

  • 1Structural Biology and Biocomputing Programme, Spanish National Cancer, Research Centre (CNIO), Madrid, Spain.

Plos Genetics
|March 4, 2014
PubMed

Insights

Certain Central Nervous System (CNS) disorders may lower cancer risk due to shared molecular pathways. This study identified specific genes and pathways deregulated in opposite directions in CNS disorders and cancers, offering new therapeutic targets.

Area of Science:

  • Neuroscience
  • Oncology
  • Genomics

Background:

  • Epidemiological studies suggest an inverse comorbidity between certain Central Nervous System (CNS) disorders and specific cancers.
  • The underlying molecular mechanisms driving this inverse relationship remain largely unexplored.

Purpose of the Study:

  • To test the hypothesis that shared molecular processes, deregulated in opposite directions, underlie the inverse comorbidity between CNS disorders and cancers.
  • To identify specific genes and pathways involved in this phenomenon.

Main Methods:

  • Transcriptomic meta-analyses were performed on data from three CNS disorders (Alzheimer's disease, Parkinson's disease, Schizophrenia) and three cancer types (Lung, Prostate, Colorectal).
  • Comparative analysis of gene expression patterns between CNS disorders and cancers was conducted.

Main Results:

  • A significant overlap was found in genes upregulated in CNS disorders and downregulated in cancers, and vice versa.
  • Opposite directional expression deregulation was also observed at the pathway level.
  • Specific genes and pathways were identified that may influence the incidence of CNS disorders and cancer risk.

Conclusions:

  • Molecular processes deregulated in opposite directions contribute to the inverse comorbidity between CNS disorders and cancers.
  • Findings support the involvement of PIN1 gene, Wnt, and P53 pathways, and highlight protein degradation pathways as potential new candidates.
  • Identified genes and pathways offer novel targets for therapeutic strategies aimed at both CNS disorders and cancer prevention/treatment.

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