بررسي ژن CKAP2 در پيشرفت سرطان كلوركتال با رويكرد زيست شناسي سامانه¬ها و بررسي آن در نمونه¬هاي بافتي بيماران مبتلا به اين سرطان

Identifying a CKAP2 gene involved in the development of colorectal cancer by systems biology approach an‎d investigating it in patients with this cancer

زيست شناسي سلولي مولكولي و ميكروبيولوژي

Introduction: Colorectal cancer (CRC) is the third most common malignancy an‎d the second leading cause of cancer-related mortality. The rapidly increasing incidence of this disease across diverse populations underscores the necessity for further research into its early diagnosis an‎d treatment. Advances in RNA sequencing technology, along with the availability of databases for storing an‎d analyzing large-scale biological data, have enabled comparative studies to identify differentially expressed genes (DEGs). In this study, transcriptomic data from colorectal cancer were obtained an‎d analyzed to identify DEGs. Subsequently, through bioinformatics analysis, a highly significant gene was identified, an‎d its differential expression was examined in both healthy an‎d tumor samples. Materials an‎d Methods: In the bioinformatics phase, bulk RNA sequencing an‎d microarray data related to CRC were retrieved. The data were then analyzed using bioinformatics tools in the R software environment. Following differential gene expression analysis, a protein-protein interaction (PPI) network was constructed for protein-coding genes, an‎d a highly interconnected gene cluster was identified using the MCODE plugin. Key genes associated with the disease were subsequently determined. To investigate the biological functions of these key genes, pathway enrichment analysis was performed using the DAVID database. In the experimental phase, the expression of the biomarker was assessed via Real-Time PCR in cancerous an‎d healthy sample groups. Results: DEGs common across three microarray datasets, along with DEGs from RNA sequencing data, were selec‎ted for PPI network construction, an‎d the most significant module for each was identified. By examining overlapping genes between the two selec‎ted modules an‎d their associated biological pathways, the gene CKAP2—which plays a role in mitotic cytokinesis an‎d microtubule stability in the mitotic spindle—was selec‎ted. Real-Time PCR analysis revealed a statistically significant LogFC of 1.5 for this gene. Additionally, ROC curve analysis demonstrated its potential as a diagnostic biomarker. Discussion: The CKAP2 gene plays a critical role in maintaining microtubule stability in the mitotic spindle an‎d is essential for proper chromosome segregation an‎d subsequent cytokinesis. Dysregulation in this pathway can lead to aneuploidy, a hallmark of most cancers. The overexpression of CKAP2 in cancer may contribute to tumor progression by disrupting regulatory proteins in this pathway, impairing chromosome separation, an‎d promoting aberrant cytokinesis. Keywords: Colorectal cancer, High-throughput biological data, RNA sequencing,

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