ADCY3: An Olfactory-Related Driver and Therapeutic Target in Kidney and Colorectal Cancers
Publisher
University of Tennessee at Chattanooga
Place of Publication
Chattanooga (Tenn.)
Abstract
Background and Objectives: Renal cell carcinoma (RCC) and colorectal cancer (CRC) are leading causes of cancer-related mortality, with limited treatment options for patients ineligible for surgery. Recent evidence highlights the emerging role of ectopic olfactory-related genes as critical regulators of tumor progression, offering a novel class of biomarkers for improved early detection and therapeutic targeting. This study aimed to identify conserved olfactory-related biomarkers and potential therapeutic targets shared between RCC and CRC.
Methodology: Four Gene Expression Omnibus (GEO) datasets (GSE66271, GSE213324, GSE142279, and GSE251845) were analyzed to identify differentially expressed genes (DEGs). Functional enrichment and protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape, with hub genes identified via cytoHubba. Expression and prognostic relevance were validated using GEPIA2, the UALCAN cancer omics portal, the Kaplan–Meier Plotter platform, and The Cancer Genome Atlas (TCGA) data. U.S. Food and Drug Administration (FDA)-approved compounds targeting candidate genes were evaluated through molecular docking. Based on the strongest predicted binding affinity, a potential drug candidate was selected for molecular dynamics (MD) simulation to assess stability and interaction dynamics. Pharmacokinetic and toxicity profiles were also analyzed.
Results: Twelve olfactory-related DEGs were consistently dysregulated across RCC and CRC datasets, with ADCY3 emerging as the central hub gene. ADCY3 was overexpressed in Kidney Renal Clear Cell Carcinoma, Colon Adenocarcinoma, and Rectum Adenocarcinoma, but showed reduced expression in Kidney Renal Papillary Cell Carcinoma. High ADCY3 expression was associated with poorer overall survival in Kidney Renal Clear Cell Carcinoma and Kidney Renal Papillary Cell Carcinoma, whereas in colon cancer cohorts, higher ADCY3 expression correlated with improved survival outcomes. Functional analyses linked ADCY3 dysregulation to cell proliferation, migration, and epithelial–mesenchymal transition. Docking studies identified rimonabant, cannabidiol, and dronabinol as potential modulators of ADCY3, with molecular dynamics simulation of the ADCY3–dronabinol complex confirming stable binding and sustained interactions.
Conclusion: ADCY3 is a conserved hub gene in RCC and CRC and represents a potential prognostic biomarker and therapeutic target. Dronabinol demonstrated stable binding in molecular dynamics simulations, supporting its potential as a therapeutic modulator, alongside rimonabant and cannabidiol, offering promising avenues for improved cancer treatment and patient outcomes.
Document Type
abstracts (summaries)
Language
English
Rights
http://rightsstatements.org/vocab/InC/1.0/
License
http://creativecommons.org/licenses/by/4.0/
Recommended Citation
Smith, Samuel; Goodson, Quin; Saha, Ayan; Das, Ankon; Islam, Md. Nur; Das Gupta, Shipan; Minkara, Maya; and Ferdoush, Jannatul, "ADCY3: An Olfactory-Related Driver and Therapeutic Target in Kidney and Colorectal Cancers". ReSEARCH Dialogues Conference proceedings. https://scholar.utc.edu/research-dialogues/2026/presentations/7.
ADCY3: An Olfactory-Related Driver and Therapeutic Target in Kidney and Colorectal Cancers
Background and Objectives: Renal cell carcinoma (RCC) and colorectal cancer (CRC) are leading causes of cancer-related mortality, with limited treatment options for patients ineligible for surgery. Recent evidence highlights the emerging role of ectopic olfactory-related genes as critical regulators of tumor progression, offering a novel class of biomarkers for improved early detection and therapeutic targeting. This study aimed to identify conserved olfactory-related biomarkers and potential therapeutic targets shared between RCC and CRC.
Methodology: Four Gene Expression Omnibus (GEO) datasets (GSE66271, GSE213324, GSE142279, and GSE251845) were analyzed to identify differentially expressed genes (DEGs). Functional enrichment and protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape, with hub genes identified via cytoHubba. Expression and prognostic relevance were validated using GEPIA2, the UALCAN cancer omics portal, the Kaplan–Meier Plotter platform, and The Cancer Genome Atlas (TCGA) data. U.S. Food and Drug Administration (FDA)-approved compounds targeting candidate genes were evaluated through molecular docking. Based on the strongest predicted binding affinity, a potential drug candidate was selected for molecular dynamics (MD) simulation to assess stability and interaction dynamics. Pharmacokinetic and toxicity profiles were also analyzed.
Results: Twelve olfactory-related DEGs were consistently dysregulated across RCC and CRC datasets, with ADCY3 emerging as the central hub gene. ADCY3 was overexpressed in Kidney Renal Clear Cell Carcinoma, Colon Adenocarcinoma, and Rectum Adenocarcinoma, but showed reduced expression in Kidney Renal Papillary Cell Carcinoma. High ADCY3 expression was associated with poorer overall survival in Kidney Renal Clear Cell Carcinoma and Kidney Renal Papillary Cell Carcinoma, whereas in colon cancer cohorts, higher ADCY3 expression correlated with improved survival outcomes. Functional analyses linked ADCY3 dysregulation to cell proliferation, migration, and epithelial–mesenchymal transition. Docking studies identified rimonabant, cannabidiol, and dronabinol as potential modulators of ADCY3, with molecular dynamics simulation of the ADCY3–dronabinol complex confirming stable binding and sustained interactions.
Conclusion: ADCY3 is a conserved hub gene in RCC and CRC and represents a potential prognostic biomarker and therapeutic target. Dronabinol demonstrated stable binding in molecular dynamics simulations, supporting its potential as a therapeutic modulator, alongside rimonabant and cannabidiol, offering promising avenues for improved cancer treatment and patient outcomes.