ArticleCancer biomarkers : section A of Disease markers2023
An integrative approach toward identification and analysis of therapeutic targets involved in HPV pathogenesis with a focus on carcinomas.
Article in Cancer biomarkers : section A of Disease markers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Unique miRomics Expression Profiles inInternational journal of molecular sciences · 2023Article
- Identification of druggable hub genes and key pathways associated with cervical cancer by protein-protein interaction analysis: An in silico study.International journal of reproductive biomedicine · 2023Article
- Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing.Biomedicines · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPersistent infection of high-risk HPVs is known to cause diverse carcinomas, mainly cervical, oropharyngeal, penile, etc. However, efficient treatment is still lacking.
objectiveIdentify and analyze potential therapeutic targets involved in HPV oncogenesis and repurposing drug candidates.
methodsIntegrative analyses were performed on the compendium of 1887 HPV infection-associated or integration-driven disrupted genes cataloged from the Open Targets Platform and HPVbase resource. Potential target genes are prioritized using STRING, Cytoscape, cytoHubba, and MCODE. Gene ontology and KEGG pathway enrichment analysis are performed. Further, TCGA cancer genomic data of CESC and HNSCC is analyzed. Moreover, regulatory networks are also deduced by employing NetworkAnalyst.
resultsWe have implemented a unique approach for identifying and prioritizing druggable targets and repurposing drug candidates against HPV oncogenesis. Overall, hundred key genes with 44 core targets were prioritized with transcription factors (TFs) and microRNAs (miRNAs) regulators pertinent to HPV pathogenesis. Genomic alteration profiling further substantiated our findings. Among identified druggable targets, TP53, NOTCH1, PIK3CA, EP300, CREBBP, EGFR, ERBB2, PTEN, and FN1 are frequently mutated in CESC and HNSCC. Furthermore, PIK3CA, CCND1, RFC4, KAT5, MYC, PTK2, EGFR, and ERBB2 show significant copy number gain, and FN1, CHEK1, CUL1, EZH2, NRAS, and H2AFX was marked for the substantial copy number loss in both carcinomas. Likewise, under-explored relevant regulators, i.e., TFs (HINFP, ARID3A, NFATC2, NKX3-2, EN1) and miRNAs (has-mir-98-5p, has-mir-24-3p, has-mir-192-5p, has-mir-519d-3p) is also identified.
conclusionsWe have identified potential therapeutic targets, transcriptional and post-transcriptional regulators to explicate HPV pathogenesis as well as potential repurposing drug candidates. This study would aid in biomarker and drug discovery against HPV-mediated carcinoma.
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