Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses

PLoS Genet. 2014 Feb 20;10(2):e1004173. doi: 10.1371/journal.pgen.1004173. eCollection 2014 Feb.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Central Nervous System / pathology
  • Comorbidity*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Peptidylprolyl Isomerase / genetics
  • Schizophrenia / epidemiology
  • Schizophrenia / genetics*
  • Schizophrenia / pathology
  • Signal Transduction

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • PIN1 protein, human
  • Peptidylprolyl Isomerase

Grants and funding

This work was supported by a Fellowship from Obra Social la Caixa grant to KI (http://obrasocial.lacaixa.es/laCaixaFoundation/home_en.html), FPI grant BES-2008-006332 to CB and grant BIO2012 to AV Group. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.