Identification of critical genes associated with radiotherapy resistance in cervical cancer by bioinformatics

Abstract

BackgroundCervical cancer (CC) is one of the common malignant tumors in women, Currently, 30% of patients with intermediate to advanced squamous cervical cancer are still uncontrolled or recurrent after standard radical simultaneous radiotherapy; therefore, the search for critical genes affecting the sensitivity of radiotherapy may lead to new strategies for treatment.MethodsFirstly, differentially expressed genes (DEGs) between radiotherapy-sensitivity and radiotherapy-resistance were identified by GEO2R from the gene expression omnibus (GEO) website, and prognosis-related genes for cervical cancer were obtained from the HPA database. Subsequently, the DAVID database analyzed gene ontology (GO). Meanwhile, the protein-protein interaction network was constructed by STRING; By online analysis of DEGs, prognostic genes, and CCDB data that are associated with cervical cancer formation through the OncoLnc database, we aim to search for the key DEGs associated with CC, Finally, the key gene(s) was further validated by immunohistochemistry.Result298 differentially expressed genes, 712 genes associated with prognosis, and 509 genes related to cervical cancer formation were found. The results of gene function analysis showed that DEGs were mainly significant in functional pathways such as variable shear and energy metabolism. By further verification, two genes, ASPH and NKAPP1 were identified through validation as genes that affect both sensitivities to radiotherapy and survival finally. Then, immunohistochemical results showed that the ASPH gene was highly expressed in the radiotherapy-resistant group and had lower Overall survival (OS) and Progression-free survival (PFS).ConclusionThis study aims to better understand the characteristics of cervical cancer radiation therapy resistance-related genes through bioinformatics and provide further research ideas for finding new mechanisms and potential therapeutic targets related to cervical cancer radiation therapy.