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

English version České info

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.

Vyšlo v časopise: Molecular Evidence for the Inverse Comorbidity between Central Nervous System Disorders and Cancers Detected by Transcriptomic Meta-analyses. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004173
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004173

Souhrn

Zdroje

1. Tabarés-SeisdedosR, DumontN, BaudotA, ValderasJM, ClimentJ, et al. (2011) No paradox, no progress: inverse cancer comorbidity in people with other complex diseases. Lancet Oncol 12: 604–608.

2. BehrensMI, SilvaM, SalechF, PonceDP, MerinoD, et al. (2012) Inverse susceptibility to oxidative death of lymphocytes obtained from Alzheimer's patients and skin cancer survivors: increased apoptosis in Alzheimer's and reduced necrosis in cancer. Series A: J Gerontol 67: 1036–1040.

3. Tabarés-SeisdedosR, RubensteinJL (2013) Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci 14: 293–304.

4. BehrensMI, LendonC, RoeCM (2009) A common biological mechanism in cancer and Alzheimer's disease? Curr Alzheimer Res 6: 196–204.

5. DevineMJ, Plun-FavreauH, WoodNW (2011) Parkinson's disease and cancer: two wars, one front. Nat Rev Cancer 11: 812–823.

6. Catalá-LópezF, Crespo-FacorroB, VietaE, ValderasJM, ValenciaA, et al. (2014) Alzheimer's Disease and Cancer: Current Epidemiological Evidence for a Mutual Protection. Neuroepidemiology 42: 121–122.

7. WestAB, DawsonVL, DawsonTM (2005) To die or grow: Parkinson's disease and cancer. Trends Neurosci 28: 348–352.

8. MusiccoM, AdorniF, Di SantoS, PrinelliF, PettenatiC, et al. (2013) Inverse occurrence of cancer and Alzheimer disease: A population-based incidence study. Neurology 81: 322–328.

9. FerreiraJJ, NeutelD, MestreT, CoelhoM, RosaMM, et al. (2010) Skin cancer and Parkinson's disease. Mov Disord 25: 139–148.

10. BajajA, DriverJA, SchernhammerES (2010) Parkinson's disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control 21: 697–707.

11. KimJS, YimSV, KohIS, ChoiJS, YooJY, et al. (2009) Single-nucleotide polymorphisms (SNPs) and haplotype analysis in vascular endothelial growth factor (VEGF) gene in the patients with Parkinson disease and lung cancer. Arch Gerontol Geriatr 48: 287–290.

12. CattsVS, CattsSV, O'TooleBI, FrostAD (2008) Cancer incidence in patients with schizophrenia and their first-degree relatives - a meta-analysis. Acta Psychiatr Scand 117: 323–336.

13. LinC-Y, LaneH-Y, ChenT-T, WuY-H, WuC-Y, et al. (2013) Inverse association between cancer risks and age in schizophrenic patients: A 12-year nationwide cohort study. Cancer sci 104: 383–390.

14. LinG-M, ChenY-J, KuoD-J, JaitehLES, WuY-C, et al. (2013) Cancer incidence in patients with schizophrenia or bipolar disorder: a nationwide population-based study in taiwan, 1997–2009. Schizophr Bull 39: 407–416.

15. DriverJA, BeiserA, AuR, KregerBE, SplanskyGL, et al. (2012) Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study. BMJ 344: e1442–e1442.

16. RoeCM, BehrensMI, XiongC, MillerJP, MorrisJC (2005) Alzheimer disease and cancer. Neurology 64: 895–898.

17. RoeCM, FitzpatrickAL, XiongC, SiehW, KullerL, et al. (2010) Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74: 106–12.

18. LuKP (2004) Pinning down cell signaling, cancer and Alzheimer's disease. Trends Biochem Sci 29: 200–209.

19. LiouY-C, ZhouXZ, LuKP (2011) Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins. Trends Biochem Sci 36: 501–514.

20. CousinE, MacéS, RocherC, DibC, MuzardG, et al. (2011) No replication of genetic association between candidate polymorphisms and Alzheimer's disease. Neurobiol Aging 32: 1443–1451.

21. CasonAL, IkeguchiY, SkinnerC, WoodTC, HoldenKR, et al. (2003) X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet 11: 937–944.

22. HuberM, PoulinR (1995) Antiproliferative effect of spermine depletion by N-cyclohexyl-1,3-diaminopropane in human breast cancer cells. Cancer Res 55: 934–943.

23. BredelM, ScholtensDM, YadavAK, AlvarezAA, RenfrowJJ, et al. (2011) NFKBIA deletion in glioblastomas. N Engl J Med 364: 627–637.

24. RamananVK, ShenL, MooreJH, SaykinAJ (2012) Pathway analysis of genomic data: concepts, methods, and prospects for future development. Trends Genet 28: 323–332.

25. KanehisaM, ArakiM, GotoS, HattoriM, HirakawaM, et al. (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36: D480–484.

26. MatthewsL, GopinathG, GillespieM, CaudyM, CroftD, et al. (2009) Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res 37: D619–22.

27. Tabarés-SeisdedosR, RubensteinJL (2009) Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14: 563–589.

28. OkerlundND, CheyetteBNR (2011) Synaptic Wnt signaling-a contributor to major psychiatric disorders? J Neurodev Disord 3: 162–174.

29. SachlosE, RisueñoRM, LarondeS, ShapovalovaZ, LeeJ-H, et al. (2012) Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell 149: 1284–1297.

30. McCallMN, JaffeeHA, IrizarryRA (2012) fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays. Bioinformatics 28: 3153–3154.

31. GautierL, CopeL, BolstadBM, IrizarryRA (2004) affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20: 307–315.

32. WangX, KangDD, ShenK, SongC, LuS, et al. (2012) An R package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection. Bioinformatics 28: 2534–2536.

33. ChoiJK, YuU, KimS, YooOJ (2003) Combining multiple microarray studies and modeling interstudy variation. Bioinformatics 19 Suppl 1: i84–90.

34. TsengGC, GhoshD, FeingoldE (2012) Comprehensive literature review and statistical considerations for microarray meta-analysis. Nucleic Acids Res 40: 3785–3799.

35. Borenstein M, Rothstein H (2009) Introduction to Meta-Analysis. 1st ed. John Wiley & Sons, New York.

36. SubramanianA, TamayoP, MoothaVK, MukherjeeS, EbertBL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102: 15545–15550.