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Gene Expression Analysis Links Autocrine Vasoactive Intestinal Peptide and ZEB1 in Gastrointestinal Cancers

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Last modified
  • 06/25/2025
Type of Material
Authors
    Ishani H Rao, Emory UniversityEdmund K Waller, Emory UniversityRohan K Dhamsania, Philadelphia College of Osteopathic Medicine (PCOM)Sanjay Chandrasekaran, University of Texas
Language
  • English
Date
  • 2023-07-01
Publisher
  • MDPI
Publication Version
Copyright Statement
  • © 2023 by the authors.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 15
Issue
  • 13
Grant/Funding Information
  • These studies were supported by funding from the Winship Cancer Institute Elkin Fellowship (SC), NIH T32 CA160040 (SC), and Abraham J. and Phyllis Katz Foundation (EKW).
Supplemental Material (URL)
Abstract
  • 0.3
  • VIP (vasoactive intestinal peptide) is a 28-amino acid peptide hormone expressed by cancer and the healthy nervous system, digestive tract, cardiovascular, and immune cell tissues. Many cancers express VIP and its surface receptors VPAC1 and VPAC2, but the role of autocrine VIP signaling in cancer as a targetable prognostic and predictive biomarker remains poorly understood. Therefore, we conducted an in silico gene expression analysis to study the mechanisms of autocrine VIP signaling in cancer. VIP expression from TCGA PANCAN tissue samples was analyzed against the expression levels of 760 cancer-associated genes. Of the 760 genes, 10 (MAPK3, ZEB1, TEK, NOS2, PTCH1 EIF4G1, GMPS, CDK2, RUVBL1, and TIMELESS) showed statistically meaningful associations with the VIP (Pearson’s R-coefficient >
  • ; p < 0.05) across all cancer histologies. The strongest association with the VIP was for the epithelial–mesenchymal transition regulator ZEB1 in gastrointestinal malignancies. Similar positive correlations between the VIP and ZEB1 expression were also observed in healthy gastrointestinal tissues. Gene set analysis indicates the VIP is involved in the EMT and cell cycle pathways, and a high VIP and ZEB1 expression is associated with higher median estimate and stromal scores These findings uncover novel mechanisms for VIP- signaling in cancer and specifically suggest a role for VIP as a biomarker of ZEB1-mediated EMT. Further studies are warranted to characterize the specific mechanism of this interaction.
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Keywords
Research Categories
  • Biology, Molecular
  • Health Sciences, Oncology

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