Theranostic Potential of EFNB2 for Cetuximab Resistance in Head and Neck Cancer

Raushan Kumar Chaudhary; Prakash Patil; Uday Venkat Mateti; Dhananjay B Alagundagi; Vijith Shetty

doi:10.1007/s12070-023-03739-9

Theranostic Potential of EFNB2 for Cetuximab Resistance in Head and Neck Cancer

Indian J Otolaryngol Head Neck Surg. 2023 Sep;75(3):1923-1936. doi: 10.1007/s12070-023-03739-9. Epub 2023 Apr 20.

Authors

Raushan Kumar Chaudhary¹, Prakash Patil², Uday Venkat Mateti¹, Dhananjay B Alagundagi², Vijith Shetty³

Affiliations

¹ Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India.
² Central Research Laboratory, K.S. Hegde Medical Academy (KSHEMA), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India.
³ Department of Medical Oncology, K.S. Hegde Medical Academy (KSHEMA), Justice K.S. Hegde Charitable Hospital, Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka 575018 India.

Abstract

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 (p < 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 IL1A, EFNB2, SPRR1A, ROBO1 and SOCS3 were the significant hub genes associated with both mRNA expression and overall survival. IL1A, ROBO1, and SOCS3 were found to be downregulated whereas EFNB2 and SPRR1A were found to be upregulated in our study. However, using UALCAN, we found that high expression of IL1A, EFNB2, SOCS3 negatively affects overall survival whereas high expression of SPRR1A and ROBO1 positively affects overall survival. Protein level for EFNB2 and SPRR1A expression was significant in tumor HNC tissue as compared to normal HNC tissue. EFNB2 was found to be a key regulator of CTX resistance among HNC patients. Targeting EFNB2 and associated PPI circuits might improve the response rate to CTX. Thus, EFNB2 has potential to be theranostic marker for CTX resistance.

Supplementary information: The online version contains supplementary material available at 10.1007/s12070-023-03739-9.

Keywords: Cetuximab; EFNB2; EGFR resistance; Hub genes; Overall survival.

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