Chaudhary Raushan Kumar, Patil Prakash, Mateti Uday Venkat, Alagundagi Dhananjay B, Shetty Vijith
Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India.
Central Research Laboratory, K.S. Hegde Medical Academy (KSHEMA), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India.
Indian J Otolaryngol Head Neck Surg. 2023 Sep;75(3):1923-1936. doi: 10.1007/s12070-023-03739-9. Epub 2023 Apr 20.
Only 13% of head and neck cancer (HNC) patients respond to cetuximab therapy despite its target (EGFR) is expressed in about 80-90% of HNC patients. However, this problem remained unresolved till date despite of numerous efforts. Thus, the current study aimed to establish hub genes involved in cetuximab resistance via series of bioinformatics approach. The GSE21483 dataset was analysed for differentially expressed genes (DEGs) using GEO2R and enrichment analysis was carried out using DAVID. STRING 11.5 and Cytoscape 3.7.2 were used for protein-protein interactions and hub genes respectively. The significant hub genes ( < 0.05) were validated using ULCAN and Human protein atlas. Validated genes were further queried for tumor infiltration using TIMER2.0. Out of total 307 DEGs, 38 hub genes were identified of which and were the significant hub genes associated with both mRNA expression and overall survival. and were found to be downregulated whereas and were found to be upregulated in our study. However, using UALCAN, we found that high expression of negatively affects overall survival whereas high expression of and positively affects overall survival. Protein level for and expression was significant in tumor HNC tissue as compared to normal HNC tissue. was found to be a key regulator of CTX resistance among HNC patients. Targeting and associated PPI circuits might improve the response rate to CTX. Thus, EFNB2 has potential to be theranostic marker for CTX resistance.
The online version contains supplementary material available at 10.1007/s12070-023-03739-9.
尽管西妥昔单抗的靶点（表皮生长因子受体，EGFR）在约80%-90%的头颈癌（HNC）患者中表达，但只有13%的头颈癌患者对西妥昔单抗治疗有反应。然而，尽管进行了大量努力，这个问题至今仍未得到解决。因此，本研究旨在通过一系列生物信息学方法确定参与西妥昔单抗耐药的关键基因。使用GEO2R分析GSE21483数据集的差异表达基因（DEG），并使用DAVID进行富集分析。分别使用STRING 11.5和Cytoscape 3.7.2进行蛋白质-蛋白质相互作用分析和确定关键基因。使用ULCAN和人类蛋白质图谱对显著的关键基因（<0.05）进行验证。使用TIMER2.0进一步查询验证基因的肿瘤浸润情况。在总共307个DEG中，确定了38个关键基因，其中[具体基因1]和[具体基因2]是与mRNA表达和总生存期相关的显著关键基因。在我们的研究中，发现[具体基因3]和[具体基因4]下调，而[具体基因5]和[具体基因6]上调。然而，使用UALCAN，我们发现[具体基因7]的高表达对总生存期有负面影响，而[具体基因8]和[具体基因9]的高表达对总生存期有正面影响。与正常头颈癌组织相比，[具体基因10]和[具体基因11]的蛋白质水平在肿瘤头颈癌组织中具有显著性。发现[具体基因12]是头颈癌患者中CTX耐药的关键调节因子。靶向[具体基因13]和相关的蛋白质-蛋白质相互作用回路可能会提高对CTX的反应率。因此，EFNB2有潜力成为CTX耐药的治疗诊断标志物。
在线版本包含可在10.1007/s12070-023-03739-9获取的补充材料。
