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 Canc...

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Main Authors: Kristina Ibáñez, César Boullosa, Rafael Tabarés-Seisdedos, Anaïs Baudot, Alfonso Valencia
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-02-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004173&type=printable
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author Kristina Ibáñez
César Boullosa
Rafael Tabarés-Seisdedos
Anaïs Baudot
Alfonso Valencia
author_facet Kristina Ibáñez
César Boullosa
Rafael Tabarés-Seisdedos
Anaïs Baudot
Alfonso Valencia
author_sort Kristina Ibáñez
collection DOAJ
description 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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spelling doaj-art-a402c59afbb0487280d9943e83b0b1922025-08-20T03:11:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-02-01102e100417310.1371/journal.pgen.1004173Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.Kristina IbáñezCésar BoullosaRafael Tabarés-SeisdedosAnaïs BaudotAlfonso ValenciaThere 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004173&type=printable
spellingShingle Kristina Ibáñez
César Boullosa
Rafael Tabarés-Seisdedos
Anaïs Baudot
Alfonso Valencia
Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
PLoS Genetics
title Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
title_full Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
title_fullStr Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
title_full_unstemmed Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
title_short Molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta-analyses.
title_sort molecular evidence for the inverse comorbidity between central nervous system disorders and cancers detected by transcriptomic meta analyses
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004173&type=printable
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AT anaisbaudot molecularevidencefortheinversecomorbiditybetweencentralnervoussystemdisordersandcancersdetectedbytranscriptomicmetaanalyses
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