Mitotic Hub Gene Network in Colorectal Cancer: Integrated Transcriptomic, Protein-Level, and Clinical-Genomic Characterization of a Ten-Gene Signature
Genes, cilt.17, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 17 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/genes17070783
- Dergi Adı: Genes
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Anahtar Kelimeler: bioinformatics, colorectal cancer, differentially expressed genes, machine learning, prognostic markers
- Erciyes Üniversitesi Adresli: Evet
Özet
Background: Colorectal cancer (CRC) remains a heterogeneous disease, and improved biomarkers are needed to support prognostic assessment. This study aimed to characterize hub genes in CRC and evaluate whether a gene signature provides biologically meaningful and prognostic information in clinical–genomic models. Methods: We integrated three GEO microarray datasets (GSE110223, GSE110224, and GSE23878) to identify common differentially expressed genes using adjusted (Formula presented.) and (Formula presented.). Hub genes and protein expression were identified through protein–protein interaction network analysis using maximal clique centrality and Human Protein Atlas, respectively. Prognostic relevance was evaluated in TCGA-COAD/READ using Kaplan–Meier analysis, multivariable Cox regression, Cox-derived prognostic indices, time-dependent ROC analysis, and regression-based machine learning for internal robustness. Principal component analysis (PCA) was used to derive a standardized PC1-based score from the 10-hub gene signature. Results: A ten-gene mitotic hub signature (TPX2, UBE2C, AURKA, NEK2, PRC1, CCNB1, CDK1, CEP55, FOXM1, and RRM2) was consistently upregulated across the three datasets and enriched for cell-cycle and mitotic pathways. Protein-level and survival analyses supported the biological relevance of several hub genes. In TCGA-COAD/READ, the signature showed limited standalone prognostic value and did not retain independent significance after adjustment for clinical variables, although it contributed modestly in integrated clinical–genomic models. PCA showed a one-dimensional signature, with PC1 capturing the dominant shared expression pattern. Gradient Boosting Regressor (R2 = 0.8035, MSE = 0.0473) supported the internal robustness of the DEG-based expression pattern. Conclusions: The ten-gene mitotic hub signature represents a coherent CRC-related proliferative program with limited value as an isolated prognostic marker, but it may still be useful as part of integrated risk models that require external validation.