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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Mitotic Hub Gene Network in Colorectal Cancer: Integrated Transcriptomic, Protein-Level, and Clinical-Genomic
Ebtihal Kamal1, Ehssan Moglad2, Samah O Mohager1
1Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia.
A ten-gene mitotic hub signature in colorectal cancer (CRC) shows limited standalone prognostic value. This signature may be useful in integrated risk models for CRC, requiring external validation for clinical application.
Area of Science:
- Genomics and Bioinformatics
- Cancer Research
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a heterogeneous disease requiring improved prognostic biomarkers.
- Current prognostic assessments need enhancement through novel molecular markers.
- Identifying key genes in CRC can lead to better patient stratification.
Purpose of the Study:
- To identify and characterize hub genes in colorectal cancer (CRC).
- To evaluate a ten-gene signature for biological relevance and prognostic information.
- To assess the utility of this signature in clinical-genomic models for CRC.
Main Methods:
- Integrated three Gene Expression Omnibus (GEO) datasets (GSE110223, GSE110224, GSE23878) to find common differentially expressed genes (DEGs).
- Utilized protein-protein interaction network analysis and the Human Protein Atlas to identify hub genes and their protein expression.
- Assessed prognostic relevance using Kaplan-Meier analysis, Cox regression, and machine learning in The Cancer Genome Atlas (TCGA-COAD/READ) data.
Main Results:
- A ten-gene mitotic hub signature (TPX2, UBE2C, AURKA, NEK2, PRC1, CCNB1, CDK1, CEP55, FOXM1, RRM2) was consistently upregulated in CRC datasets.
- The signature is enriched for cell-cycle and mitotic pathways, with protein-level data supporting biological relevance.
- The signature demonstrated limited standalone prognostic value in TCGA-COAD/READ but contributed modestly in integrated clinical-genomic models.
Conclusions:
- The ten-gene mitotic hub signature represents a coherent proliferative program in CRC.
- This signature has limited value as an isolated prognostic marker.
- The signature may be beneficial within integrated risk models for CRC, pending external validation.
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