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

Abstract

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. 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. 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. These shared transcriptomic alterations could help explain epidemiological observations suggesting direct and inverse comorbid associations between ASD and particular cancer types.

The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice

“…More recent studies have suggested that EPHB6 is a candidate ASD-associated gene [ 14 – 16 ], and recent genomic studies have found that EPHB6 is mutated in some ASD patients [ 17 , 18 ]. Most importantly, transcriptome analyses have shown that EPHB6 is downregulated in ASD patients [ 19 , 20 ]. Although EPHB6 plays an important role in regulating Eph receptor signaling networks, T cell functions, development of intestinal epithelium, and epithelial homeostasis [ 21 – 23 ], the role and mechanisms of EPHB6 involved in regulation of the gut microbiota and ASD remain unclear.…”

Comprehensive Analysis of RNA-Seq Gene Expression Profiling of Brain Transcriptomes Reveals Novel Genes, Regulators, and Pathways in Autism Spectrum Disorder

“…Previous studies found that several candidate genes demonstrated differential expression of ASD patients in brain and blood, as compared to healthy controls [ 4 , 5 , 6 , 7 , 8 , 9 ]. Despite some important data having been obtained from previous analyses [ 4 , 10 ], we here applied a System Biology approach to further deepen the understanding of the pathophysiological mechanisms in ASD. In this study, two independent publicly available ASD brain studies were used to perform a meta-analysis aimed at identifying novel ASD candidate genes.…”

Gut microbiota regulates autism-like behavior by mediating vitamin B6 metabolism in EphB6-deficient mice

“…First in our study, we uncover EphB6 is an ASD-associated gene functionally. EPHB6 has been suggested as a candidate gene for ASD for a long time [15][16][17] and is found to be down-regulated in ASD patients [19,20]. Here, using our transgenic mouse models, we found deletion of EphB6 induced autism-like behavior in mice that mimicked the core symptoms of ASD patients fairly well.…”

“…After that, more studies suggested EPHB6 as a candidate of ASD-associated-gene [14][15][16] and recent genomic studies have found the mutation of EPHB6 in some ASD patients [17,18]. Most importantly, EPHB6 has been found to be with a down-regulated expression in ASD patients in transcriptome analysis [19,20]. Although EPHB6 plays an important role in regulating Eph receptor signaling networks, T cell functions, development of intestinal epithelium and epithelial homeostasis [21][22][23], the role and mechanisms of EPHB6 involved in regulating gut microbiota and ASD are still unclear.…”