Kožik Bojana, Čorbo Tarik, Pojskić Naris, Božović Ana, Todorović Lidija, Kolaković Ana, Mandušić Vesna, Pojskić Lejla
Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11000 Belgrade, Serbia.
Laboratory for Bioinformatics and Biostatistics, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina.
Int J Mol Sci. 2025 Jun 28;26(13):6261. doi: 10.3390/ijms26136261.
Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways most likely associated with VI in rectal carcinoma. As showed statistically significant negative relations with the VI in RC patients, we further analyzed its top co-dependent genes-DNAL4, EVI2B, PPP1R35, PTGR3, RPL21, SOX4, and ZNF3-for the experimentally proven molecular modulators. We identified a total of 23 compounds from the Comparative Toxicogenomics Database based on previously reported data for all eight target genes. The search was expanded to include additional chemical agents by structure similarity using the PubChem database, which revealed 9661 additional compounds. These were subsequently used for molecular interaction analysis against target proteins co-expressed with, or associated with, in RC with VI. Ultimately, we identified four high-affinity compounds-cyanoginosin LR, doxorubicin, benzo[a]pyrene, and dibenzo(a,e)pyrene-that interacted with all target proteins. These compounds show potential for further assessment of their role in modulating processes related to vascular invasion, which is a strong negative predictor of RC outcomes.
直肠癌（RC）约占所有结直肠癌（CRC）的30%，被视为一种独特的临床实体。血管侵犯（VI）被认为是直肠癌预后不良的独立预测因素。在本研究中，我们应用生物信息学方法来识别直肠癌中最可能与VI相关的基因通路。由于其在直肠癌患者中与VI呈统计学显著负相关，我们进一步分析了其顶级共依赖基因——DNAL4、EVI2B、PPP1R35、PTGR3、RPL21、SOX4和ZNF3——以寻找经实验证实的分子调节剂。基于之前报道的所有八个靶基因的数据，我们从比较毒理基因组学数据库中总共鉴定出23种化合物。利用PubChem数据库通过结构相似性将搜索范围扩大到包括其他化学试剂，结果又发现了9661种化合物。随后，这些化合物被用于针对与直肠癌伴VI中共同表达或相关的靶蛋白进行分子相互作用分析。最终，我们鉴定出四种高亲和力化合物——蓝藻毒素LR、阿霉素、苯并[a]芘和二苯并(a,e)芘——它们与所有靶蛋白相互作用。这些化合物在进一步评估其在调节与血管侵犯相关过程中的作用方面显示出潜力，而血管侵犯是直肠癌预后的一个强有力的负性预测因素。
