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Vol 29, No 6 (2024)
Research paper
Published online: 2025-01-17

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AURKAPS1, HERC2P2 and SDHAP1 pseudogenes: molecular role in development and progression of head and neck squamous cell carcinomas and their diagnostic utility

Tomasz Kolenda12, Joanna Kozłowska-Masłoń34, Patrycja Mantaj5, Nina Grzejda46, Kacper Kamiński789, Maria Dziuba10, Małgorzata Czarnecka10, Aleksandra Leszczyńska10, Paulina Poter1112, Kacper Guglas4, Klaudia Dudek134, Katarzyna Regulska142, Paulina Gieremek1415, Beata Stanisz15, Anna Florczak-Substyk10, Marlena Janiczek-Polewska1617, Urszula Kazimierczak18, Katarzyna Lamperska24, Zefiryn Cybulski192, Anna Teresiak24
DOI: 10.5603/rpor.104016
Rep Pract Oncol Radiother 2024;29(6):718-731.

Abstract

Background: Pseudogenes are epigenetic elements whose function is mostly unknown in cancer including head and neck cancers (HNSCCs). In our study we analyzed selected three pseudogenes, aurora kinase A pseudogene 1 (AURKAPS1), hect domain and RLD 2 pseudogene 2 (HERC2P2) and succinate dehydrogenase complex flavoprotein subunit A pseudogene 1 (SDHAP1), in the context of molecular function, biological role and potential utility as a biomarker in HNSCCs.

Materials and methods: Based on The Cancer Genome Atlas (TCGA) data we checked potential association of pseudogenes with pathological and clinical features, survival, cellular phenotype and involvement in pathways and cellular processes, and association with patients' response to radiotherapy.

Results: Only AURKAPS1 pseudogene has significant upregulation in cancer than in normal samples and could be used as a diagnostic biomarker. Expression levels of all pseudogenes are dependent on cancer localization. SDHAP1 are the most differentiated and associated with tumor subtypes, expressions of AURKAPS1 do not depend on this tumor classification. Higher expression levels of AURKAPS1, HERC2P2 and SDHAP1 were associated with more aggressive phenotypes and associated with important cellular pathways and biological processes. Moreover, we observed that the expression of all pseudogenes were higher in human papilloma virus (HPV)(+) than in HPV(–) patients. Only AURKAPS1 was associated with higher genome instability and worse response to radiotherapy. Patients with higher expression levels of AURKAPS1 and HERC2P2 displayed better survival.

Conclusions:  AURKAPS1 is a potential biomarker for HNSCC patients. This pseudogene is associated with changes in DNA repair, which should be more deeply analyzed in the future.

Keywords: HNSCCpseudogenelncRNAbiomarkerHPVoncogenesuppressornon-coding RNATCGA

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