Rodríguez-García Marta, Burgos-Molina Antonio M, González-Vidal Alejandro, Sendra-Portero Francisco, Bernal Manuel, Ruiz-Gómez Miguel J
Departamento de Radiología y Medicina Física, Universidad de Málaga, Málaga, España.
Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Universidad de Málaga, Málaga, España.
Int J Radiat Biol. 2025;101(7):685-697. doi: 10.1080/09553002.2025.2496079. Epub 2025 Apr 28.
The development of radiation resistance by tumor cells severely affects the survival of colorectal cancer patients. The aim of this work is to study the molecular mechanisms involved in the resistance to radiotherapy treatment in colorectal cancer and the identification of key genes as possible biomarkers.
Data mining was performed in PubMed with the keywords 'colorectal neoplasms', 'radiotherapy', and 'resistance', generating a total of 242 articles in which a series of inclusion and exclusion criteria were applied to select the articles of interest. Then, an in-silico analysis of the selected genes was performed with the bioinformatic tools: GeneCodis, Metascape, KEGG, REACTOME, STRING, STITCH, CHEA3, DGIdb, CTD, and GEPIA.
Different mechanisms and genes involved in radiation resistance were described. These are related to evasion of apoptosis, cell cycle dysregulation, epithelial-mesenchymal transition, and repair of DNA breaks, with the last one being the most relevant and influential. The In-silico study carried out with 21 genes involved in radiation resistance showed the implication of FoxO signaling and EGFR tyrosine kinase inhibitor resistance as the most enriched pathways. In addition, the study identified the key proteins AURKA, BIRC5, and PLK1, showing multiple interacting chemicals and drugs; such as tamoxifen, omacetaxine mepesuccinate, and hydroxyzine pamoate, among others.
The identification of multiple transcription factors that regulate the expression of these key genes as well as the validation in patient samples where higher expression is observed in tumor patients, conserved across tumor stages I-IV, suggests their potential as possible biomarkers.
肿瘤细胞抗辐射能力的发展严重影响结直肠癌患者的生存。本研究旨在探讨结直肠癌放疗抵抗的分子机制，并鉴定关键基因作为潜在的生物标志物。
在PubMed数据库中使用关键词“结直肠肿瘤”“放射治疗”和“抵抗”进行数据挖掘，共检索到242篇文章，通过一系列纳入和排除标准筛选出感兴趣的文章。然后，使用生物信息学工具GeneCodis、Metascape、KEGG、REACTOME、STRING、STITCH、CHEA3、DGIdb、CTD和GEPIA对所选基因进行电子分析。
描述了与辐射抵抗相关的不同机制和基因。这些机制与细胞凋亡逃避、细胞周期失调、上皮-间质转化以及DNA断裂修复有关，其中DNA断裂修复最为相关且具有影响力。对21个参与辐射抵抗的基因进行的电子研究表明，FoxO信号通路和表皮生长因子受体酪氨酸激酶抑制剂抵抗是最富集的通路。此外，该研究还鉴定出关键蛋白极光激酶A（AURKA）、杆状病毒IAP重复序列包含蛋白5（BIRC5）和 polo样激酶1（PLK1），显示出多种相互作用的化学物质和药物，如他莫昔芬、奥马西他辛甲磺酸盐和羟嗪帕莫酸盐等。
鉴定出多个调控这些关键基因表达的转录因子，并在肿瘤患者中观察到较高表达且在I-IV期肿瘤中均保守的患者样本中进行验证，表明它们有可能作为生物标志物。
