Bioinformatics Analysis Reveals Distinct Oncogenic Profiles of HPV-16 and HPT-18 to Other Subtypes in Cervical Cancer

Document Type : Research Articles

Authors

1 Division of Oncogynecology, Department of Obstetrics and Gynecology, Prof. Dr. I.G.N.G. Ngoerah Hospital, Denpasar, Bali, Indonesia.

2 Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.

3 Faculty of Medicine, Udayana University, Bali, Indonesia.

4 Department of Obstetrics and Gynecology, Faculty of Medicine, Udayana University, Bali, Indonesia.

Abstract

Background: HPV types 16 and 18 are associated with 70% of invasive cervical cancers. Between these two types of HPV, HPV type 16 is more commonly found in cervical cancer patients, whereas HPV type 18 is less frequently reported. Currently, the molecular mechanism underlying the increased cancer risk in HPV type 16, compared to HPV type 18, has not yet been fully elucidated. Objective: This paper aims to identify the factors that make HPV type 16 the primary contributor to cervical cancer by comparing gene expression profiles with those of HPV type 18. Method: The examination began after obtaining the RNA sequencing dataset (GSE192897). The dataset’s genes were then analyzed to identify differentially expressed genes (DEGs) using the GEO2R tool. With the help of Enrichr and SRplot tools, the DEGs were first enriched and analyzed through Gene Ontology (GO), GeDiPNet, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, a protein–protein interaction (PPI) network was constructed using Cytoscape, and the top ten hub genes were ranked with the help of CytoHubba. Result: DEG analysis revealed 128 differentially expressed genes (DEGs), including 14 upregulated and 114 downregulated genes. The upregulated genes were associated with positive regulation of interferon-beta production, vesicle-related processes, endopeptidase inhibitor activity, and interferon-gamma signaling. The downregulated genes were linked to positive regulation of cell motility, the endoplasmic reticulum lumen, cytokine activity, and signal transduction. Discussion: There are several differentially expressed genes (DEGs) in HPV type 16 compared to type 18; these upregulated genes may potentially play a role in promoting cervical cancer development more significantly than HPV type 18. These DEGs underscore the urgency of implementing HPV genotyping tests to identify HPV types with higher cervical cancer prevalence. Conclusion: This analysis identified BUB1, DLGAP5, and ASPM as key genes specifically expressed in HPV-16/18–related cervical cancer, suggesting their potential as biomarkers for prognosis and disease progression.

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