Integrative analysis of the rare endocrine cancers using multi-omics data

Authors

• SV Daulatabad
• A Jain
• D Nousome
• M Tandon
• D Varghese
• K Pendo
• MFW Malone
• J del Rivero
• BC Widemann
• KM Reilly

Abstract

Endocrine cancers, including thyroid, adrenal, pituitary, and endocrine pancreatic cancers, are rare and understudied due to limited biospecimens and genomic data. We employed multi-omics approaches—RNA sequencing, whole-exome sequencing, and whole-genome sequencing—to elucidate molecular signatures and regulatory pathways in these cancers. We identified genes specific to various endocrine cancers, such as GNRHR, MMP9/12/13, TPH1, SLC6A2, and DRD2. Co-expression network analysis revealed distinct neuronal pathways associated with cancer progression. Integrating protein-protein interaction and multi-omic aberrant gene interaction networks, we discovered pathways involving noradrenaline biosynthesis in pheochromocytomas and calcitonin regulation in medullary thyroid carcinoma. Additionally, alternatively spliced genes in endocrine cancers were enriched in cancer hallmarks, including genomic instability. Our comprehensive multi-omic analysis offers novel insights into candidate therapeutic targets for these rare endocrine cancers.

Scientific Focus Area: Computational Biology

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