Format

Send to

Choose Destination
Mol Autism. 2019 Apr 8;10:17. doi: 10.1186/s13229-019-0262-8. eCollection 2019.

Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer.

Author information

1
1Biomedical Research Networking Center of Mental Health (CIBERSAM), Madrid, Spain.
2
2Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, University of Valencia, Blasco-Ibañez 15, 46010 Valencia, Spain.
3
3INCLIVA Health Research Institute, Valencia, Spain.
4
4Department of Health Planning and Economics, National School of Public Health/IMIENS, Institute of Health Carlos III, Madrid, Spain.
5
5Barcelona Supercomputing Center (BSC), Barcelona, Spain.
6
6Genomics England, London, UK.
7
7Structural Biology Program, Spanish National Cancer Research Program (CNIO), Madrid, Spain.
8
8Anthropology Section, Department of Evolutionary Biology, Ecology and Environmental Sciences, Biomedicine Institute (IBUB), University of Barcelona (UB), Barcelona, Spain.
9
9Departamento de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Calle Ramon y Cajal s/n 46115 Alfara del Patriarca, Valencia, Spain.
10
Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.
11
11Aix-Marseille Univ, Inserm, MMG, Marseille Medical Genetics, Marseille, France.
12
12Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824 USA.
13
13Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, CA 94158 USA.
14
14Department of Psychiatry, University of California, San Francisco, CA 94158 USA.
15
15Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.

Abstract

Background:

Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported.

Methods:

Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis and report gene, pathway, and drug set-based overlaps between them.

Results:

Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD.

Conclusions:

Comparisons of ASD and cancer differential gene expression meta-analysis results suggest that brain, kidney, thyroid, and pancreatic cancers are candidates for direct comorbid associations with ASD. On the other hand, lung and prostate cancers are candidates for inverse comorbid associations with ASD. Joint perturbations in a set of specific biological processes underlie these associations which include several pathways previously implicated in both cancer and ASD encompassing immune system alterations, impairments of energy metabolism, cell cycle, and signaling through PI3K and G protein-coupled receptors among others. These findings could help to explain epidemiological observations pointing towards direct and inverse comorbid associations between ASD and specific cancer types and depict a complex scenario regarding the molecular patterns of association between ASD and cancer.

KEYWORDS:

ASD; Autism; Cancer; Comorbidity; Gene expression; Meta-analysis; Multimorbidity; Transcriptome

PMID:
31007884
PMCID:
PMC6454734
DOI:
10.1186/s13229-019-0262-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center