The roles of FGFR, EGFR and AMP-activated protein kinase pathway in colorectal cancer stem cells derived spheroids: Implications in colorectal cancer treatment | [Asian Journal of Agriculture and Biology • 2025]

Author(s):

1. Mahmood Rasool: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University,Jeddah,Saudi Arabia

2. Khalid I Alhassan: Department of Biological Science, King Abdulaziz University,Jeddah,Saudi Arabia

3. Sajjad Karim: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University,Jeddah,Saudi Arabia

4. Absarul Haque: King Fahd Medical Research Center, Faculty of Applied Medical Sciences, King Abdulaziz University,Jeddah,Saudi Arabia

5. Mohammed HZ Mutwakil: Department of Biological Science, King Abdulaziz University,Jeddah,Saudi Arabia

6. Mohammed Alharthi: Faculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz University,Jeddah,Saudi Arabia

7. Adeel G Chaudhary: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University,Jeddah,Saudi Arabia

8. Peter Natesan Pushparaj: Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University,Jeddah,Saudi Arabia

Abstract:

The aim of our research was to identify molecular targets that can be targeted by drugs and patient-specific models for personalized medicine for colorectal cancer (CRC). Here, we obtained high-throughput RNA sequencing data from Gene Expression Omnibus (GEO) with accession number GSE205787 and analyzed it using next-generation knowledge discovery tools such as BioJupies and Ingenuity Pathway Analysis (IPA) software. Differentially expressed genes (DEGs) were identified by comparing the raw counts from 47 CRC patient-derived spheroids (CRC-CSCs) with those from normal spheroids from the epithelium of the colon and rectum of healthy individuals, using BioJupies tools. IPA was used to identify differentially regulated canonical pathways, upstream regulators of CRC, non-directional networks, diseases, and biofunctions, as well as to conduct subsequent perturbation analysis using the Molecular Prediction Analysis (MAP) tool. Our study demonstrates that several KEGG pathways, including the AMPK, Phospholipase D, MAPK, and PI3-AKT signaling pathways, were significantly downregulated in the CRC-CSC group. Additionally, Wnt signaling and FGFR pathways were significantly upregulated. Moreover, according to Wikipathways, the EGF/EGFR signaling pathway, MAPK signaling pathway, G-protein signaling pathway, and Focal Adhesion-PI3-AKT pathway were downregulated in the CRC-CSC group. Furthermore, based on the Reactome, the Metabolism, Vesicle-mediated transport, RAF signaling, and Galpha (12/13) signaling pathways were also downregulated in the CRC-CSC group. Utilizing innovative drug combination approaches and innovative drug delivery techniques, CRC treatments can be enhanced by modulating the FGFR, EGFR, and AMPK signaling pathways, which may ultimately lead to improved patient outcomes.

Page(s): 1-11

DOI: 10.35495/ajab.2023.365

Published: Journal: Asian Journal of Agriculture and Biology, Volume: 1, Issue: 1, Year: 2025

Keywords:

colorectal cancer , Epidermal growth factor receptor , Cancer stem cell spheroids , BioJupies , Ingenuity Pathway Analysis , Fibroblast Growth Factor Receptor , AMPactivated protein kinase signaling

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