Laham Amina Jamal, El-Awady Raafat, Lebrun Jean-Jacques, Ayad Maha Saber
Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
Cancers (Basel). 2022 Apr 18;14(8):2034. doi: 10.3390/cancers14082034.
Colorectal cancer (CRC) is the third most common cancer worldwide and has an increasing incidence in younger populations. The dual-specificity tyrosine-regulated kinase (DYRK) family has been implicated in various diseases, including cancer. However, the role and contribution of the distinct family members in regulating CRC tumorigenesis has not been addressed yet. Herein, we used publicly available CRC patient datasets (TCGA RNA sequence) and several bioinformatics webtools to perform in silico analysis (GTEx, GENT2, GEPIA2, cBioPortal, GSCALite, TIMER2, and UALCAN). We aimed to investigate the family member expression pattern, prognostic value, and oncological roles in CRC. This study shed light on the role of distinct DYRK family members in CRC and their potential outcome predictive value. Based on mRNA level, is upregulated in late tumor stages, with lymph node and distant metastasis. All DYRKs were found to be implicated in cancer-associated pathways, indicating their key role in CRC pathogenesis. No significant mutations were identified, suggesting that expression variation in normal vs. tumor samples is likely linked to epigenetic regulation. The expression of and expression correlated with immune-infiltrating cells in the tumor microenvironment and was upregulated in MSI subtypes, pointing to their potential role as biomarkers for immunotherapy. This comprehensive bioinformatics analysis will set directions for future biological studies to further exploit the molecular basis of these findings and explore the potential of DYRK1A modulation as a novel targeted therapy for CRC.
结直肠癌(CRC)是全球第三大常见癌症,且在年轻人群中的发病率呈上升趋势。双特异性酪氨酸调节激酶(DYRK)家族与包括癌症在内的多种疾病有关。然而,该家族不同成员在调节CRC肿瘤发生中的作用和贡献尚未得到研究。在此,我们使用公开可用的CRC患者数据集(TCGA RNA序列)和几个生物信息学网络工具进行了计算机分析(GTEx、GENT2、GEPIA2、cBioPortal、GSCALite、TIMER2和UALCAN)。我们旨在研究该家族成员在CRC中的表达模式、预后价值和肿瘤学作用。这项研究揭示了不同DYRK家族成员在CRC中的作用及其潜在的预后预测价值。基于mRNA水平,[此处原文可能缺失具体基因名称]在肿瘤晚期、伴有淋巴结和远处转移时上调。所有DYRK均被发现与癌症相关通路有关,表明它们在CRC发病机制中起关键作用。未发现显著的[此处原文可能缺失具体基因名称]突变,这表明正常样本与肿瘤样本中[此处原文可能缺失具体基因名称]的表达差异可能与表观遗传调控有关。[此处原文可能缺失具体基因名称]的表达与肿瘤微环境中的免疫浸润细胞相关,且在微卫星高度不稳定(MSI)亚型中上调,表明它们作为免疫治疗生物标志物的潜在作用。这种全面的生物信息学分析将为未来的生物学研究指明方向,以进一步探究这些发现的分子基础,并探索DYRK1A调节作为CRC新型靶向治疗的潜力。