Inverse Comorbidity between Down Syndrome and Solid Tumors: Insights from In Silico Analyses of Down Syndrome Critical Region Genes

Author:

Fosu Kwadwo12,Quarshie Jude Tetteh1,Sarpong Kwabena Amofa Nketia12,Aikins Anastasia Rosebud12ORCID

Affiliation:

1. Department of Biochemistry Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Accra P.O. Box LG 54, Ghana

2. West African Centre for Cell Biology of Infectious Pathogens, Legon, Accra P.O. Box LG 54, Ghana

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.

Funder

World Bank African Centres of Excellence Impact

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

Reference51 articles.

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