Chasib Mezher Rawaa, Azari Hanieh, Khayami Reza, Fiuji Hamid, Alizadeh Farzaneh, Goshayeshi Ladan, Rajabian Majid, Saeed Gataa Ibrahim, Mahdi Hassanian Seyed, Avan Amir
Metabolic Syndrome Research Center Mashhad University of Medical Sciences Mashhad Iran.
Department of Medical Biochemistry Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran.
J Cell Commun Signal. 2025 Aug 27;19(3):e70042. doi: 10.1002/ccs3.70042. eCollection 2025 Sep.
Cancer remains a major global health challenge, with high prevalence and mortality rates emphasizing the urgent need for innovative treatment strategies. Although precision oncology offers tailored therapies based on genetic profiles, the clinical translation of genomic insights has been slow. Drug repurposing, using existing FDA-approved drugs for new indications, presents a cost-effective and time-efficient alternative. This study investigates as a potential direct target of alpha-glucosidase inhibitors in colorectal cancer (CRC), explores its biomarker potential, and evaluates gene expression patterns across diverse cancers. Using RNA-Seq data from Recount3, Firebrowse, and gene set co-expression analysis databases, we analyzed the differential expression of and its paralog across 33 cancer types. We examined mutation profiles, methylation status, survival impact, immune cell infiltration, and drug-mRNA interactions. Validation was performed via real-time PCR and whole-exome sequencing (WES) in CRC patients. and showed differential expression across multiple cancers, with upregulated and downregulated in gastrointestinal tumors. Both genes were linked to key cancer-related pathways, including metabolism, apoptosis, cell cycle regulation, and epithelial-mesenchymal transition. exhibited frequent mutations and aberrant methylation in several cancers. Their expression correlated with immune cell infiltration and drug sensitivity, highlighting potential for therapy planning. Diagnostic modeling showed over 80% accuracy. In CRC patients, downregulation was confirmed in 64 samples, and WES revealed a novel mutation (rs2960746). These findings underscore and as promising biomarkers and therapeutic targets, supporting their relevance in advancing personalized oncology.
癌症仍然是一项重大的全球健康挑战,其高发病率和死亡率凸显了对创新治疗策略的迫切需求。尽管精准肿瘤学提供了基于基因图谱的个性化疗法,但基因组见解在临床中的转化一直很缓慢。药物重新利用,即将现有的美国食品药品监督管理局(FDA)批准的药物用于新的适应症,是一种具有成本效益且高效省时的替代方法。本研究调查了[具体内容]作为结直肠癌(CRC)中α-葡萄糖苷酶抑制剂的潜在直接靶点,探索其作为生物标志物的潜力,并评估其在多种癌症中的基因表达模式。利用来自Recount3、Firebrowse和基因集共表达分析数据库的RNA测序数据,我们分析了[具体基因]及其旁系同源基因在33种癌症类型中的差异表达。我们检查了突变谱、甲基化状态、生存影响、免疫细胞浸润以及药物与mRNA的相互作用。通过实时PCR和全外显子测序(WES)在CRC患者中进行了验证。[具体基因]在多种癌症中表现出差异表达,在胃肠道肿瘤中[具体基因1]上调而[具体基因2]下调。这两个基因都与关键的癌症相关通路有关,包括代谢、凋亡、细胞周期调控和上皮-间质转化。[具体基因]在几种癌症中表现出频繁的突变和异常甲基化。它们的表达与免疫细胞浸润和药物敏感性相关,突出了其在治疗规划中的潜力。诊断模型显示准确率超过80%。在CRC患者中,在64个样本中证实了[具体基因]的下调,WES揭示了一个新的[具体基因]突变(rs2960746)。这些发现强调了[具体基因]作为有前景的生物标志物和治疗靶点,支持它们在推进个性化肿瘤学方面的相关性。