{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:46:29Z","timestamp":1785433589485,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","award":["PSAU\/2025\/03\/33476"],"award-info":[{"award-number":["PSAU\/2025\/03\/33476"]}],"id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PSAU\/2025\/03\/33476"],"award-info":[{"award-number":["PSAU\/2025\/03\/33476"]}],"id":[{"id":"https:\/\/ror.org\/04jt46d36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2013genomic models. Methods: We integrated three GEO microarray datasets (GSE110223, GSE110224, and GSE23878) to identify common differentially expressed genes using adjusted p&lt;0.05 and \u2223log2FC\u2223&gt;1. Hub genes and protein expression were identified through protein\u2013protein interaction network analysis using maximal clique centrality and Human Protein Atlas, respectively. Prognostic relevance was evaluated in TCGA-COAD\/READ using Kaplan\u2013Meier 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\u2013genomic 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.<\/jats:p>","DOI":"10.3390\/genes17070783","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitotic Hub Gene Network in Colorectal Cancer: Integrated Transcriptomic, Protein-Level, and Clinical-Genomic Characterization of a Ten-Gene Signature"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6081-2615","authenticated-orcid":false,"given":"Ebtihal","family":"Kamal","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehssan","family":"Moglad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah O.","family":"Mohager","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6906-1553","authenticated-orcid":false,"given":"Mehad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mobarak Mahfod","family":"Aldoseri","sequence":"additional","affiliation":[{"name":"College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barakat A. Al","family":"Suwayyid","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-0679","authenticated-orcid":false,"given":"Azizah Salim","family":"Bawadood","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-8239","authenticated-orcid":false,"given":"Hamdan Z.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Qassim University, P.O. Box 6655, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6323-3288","authenticated-orcid":false,"given":"Mikail","family":"Akbulut","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., Lim, Y.C., Kibria, K.M.K., Mohiuddin, A.K.M., and Ming, L.C. (2022). 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