Abstract
Cervical cancer as a common gynecological malignancy threatens the health and lives of women. Resistance to radiotherapy is the primary cause of treatment failure and is mainly related to difference in the inherent vulnerability of tumors after radiotherapy. Here, we investigated signature genes associated with poor response to radiotherapy by analyzing an independent cervical cancer dataset from the Gene Expression Omnibus, including pre-irradiation and mid-irradiation information. A total of 316 differentially expressed genes were significantly identified. The correlations between these genes were investigated through the Pearson correlation analysis. Subsequently, random forest model was used in determining cancer-related genes, and all genes were ranked by random forest scoring. The top 30 candidate genes were selected for uncovering their biological functions. Functional enrichment analysis revealed that the biological functions chiefly enriched in tumor immune responses, such as cellular defense response, negative regulation of immune system process, T cell activation, neutrophil activation involved in immune response, regulation of antigen processing and presentation, and peptidyl-tyrosine autophosphorylation. Finally, the top 30 genes were screened and analyzed through literature verification. After validation, 10 genes (KLRK1, LCK, KIF20A, CD247, FASLG, CD163, ZAP70, CD8B, ZNF683, and F10) were to our objective. Overall, the present research confirmed that integrated bioinformatics methods can contribute to the understanding of the molecular mechanisms and potential therapeutic targets underlying radiotherapy resistance in cervical cancer.
Highlights
Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancerrelated mortality in women globally (Barker et al, 2015; Doja et al, 2020; Sahu and Pattanayak, 2020)
After obtaining 30 candidate genes, we extensively reviewed the literature to determine whether the selected genes are signature genes for cervical cancer radiotherapy resistance
Pearson correlation analysis was subsequently performed between 316 differential genes for the assessment of the association (Cheng et al, 2019)
Summary
Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancerrelated mortality in women globally (Barker et al, 2015; Doja et al, 2020; Sahu and Pattanayak, 2020). Among women between the ages of 20 and 39, cervical cancer is the second leading cause of cancer deaths (Siegel et al, 2020). Approximately 80% of patients with cervical cancer need radiotherapy in the process of treatment (Jemal et al, 2011). Cisplatin increases the incidence of acute hematological toxicity, which may lead to the interruption of CCRT treatment and poor prognosis in patients with cervical cancer (Green et al, 2001; Dueñas-González et al, 2011; Bazan et al, 2013; Liu et al, 2020). The 5 years survival rate for advanced cervical cancer is still only 5–15% (Chopra et al, 2018). Exploring the mechanisms underlying radiosensitivity at the molecular level is the essential strategy for increasing long-term survival of cervical cancer
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