Inverse Comorbidity between Down Syndrome and Solid Tumors: Insights from In Silico Analyses of Down Syndrome Critical Region Genes
Date
2023
Journal Title
Journal ISSN
Volume Title
Publisher
Genes
Abstract
An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors
such as breast and lung cancers, and it is posited that the overexpression of genes within the Down
Syndrome Critical Region (DSCR) of human chromosome 21 may account for this phenomenon.
By analyzing publicly available DS mouse model transcriptomics data, we aimed to identify DSCR
genes that may protect against human breast and lung cancers. Gene expression analyses with
GEPIA2 and UALCAN showed that DSCR genes ETS2 and RCAN1 are significantly downregulated
in breast and lung cancers, and their expression levels are higher in triple-negative compared to
luminal and HER2-positive breast cancers. KM Plotter showed that low levels of ETS2 and RCAN1
are associated with poor survival outcomes in breast and lung cancers. Correlation analyses using
OncoDB revealed that both genes are positively correlated in breast and lung cancers, suggesting
that they are co-expressed and perhaps have complementary functions. Functional enrichment
analyses using LinkedOmics also demonstrated that ETS2 and RCAN1 expression correlates with
T-cell receptor signaling, regulation of immunological synapses, TGF-β signaling, EGFR signaling,
IFN-γ signaling, TNF signaling, angiogenesis, and the p53 pathway. Altogether, ETS2 and RCAN1
may be essential for the development of breast and lung cancers. Experimental validation of their
biological functions may further unravel their roles in DS and breast and lung cancers
Description
Research Article
Keywords
down syndrome, breast cancer, lung cancer
Citation
Citation: Fosu, K.; Quarshie, J.T.; Sarpong, K.A.N.; Aikins, A.R. Inverse Comorbidity between Down Syndrome and Solid Tumors: Insights from In Silico Analyses of Down Syndrome Critical Region Genes. Genes 2023, 14, 800. https:// doi.org/10.3390/genes14040800