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  • Introduction of AOX1 gene as an effective gene in tumorigenesis in thyroid papillary carcinoma

  • shaghayegh khademi,1 Seyed-Morteza Javadirad,2,* Mohsen Kolahdouzan,3
    1. MS Student, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
    2. Assistant professor, Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan,Isfahan, Iran
    3. Associate professor, Department of surgery, Faculty of medicine, Isfahan University of medical sciences, Isfahan, Iran


  • Introduction: Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer and is marked by varied clinical behavior along with a complicated molecular profile. While PTC typically shows a positive outlook, characterized by slow growth, effective differentiation, and a mild clinical progression, some subtypes demonstrate more aggressive traits and are linked to a higher likelihood of recurrence after surgery. The molecular mechanisms involved in PTC etiology are not fully understood, hindering our comprehension of disease pathogenesis and leading to difficulties in early diagnosis and efficient treatment.
  • Methods: For a more thorough insight into the molecular mechanisms underlying PTC pathogenesis, RNA sequencing (RNA-seq) transcriptomic data was obtained from The Cancer Genome Atlas (TCGA) database. Differential gene expression analysis was performed for all annotated genes using the DESeq2 statistical package, and the most significant target gene was chosen. Functional enrichment analyses, including Gene Ontology (GO) and Reactome pathway analyses, were conducted using Enrichr. GEO Disease Perturbations was used to identify diseases associated with the target gene expression. An extensive cancer study was carried out to investigate the expression pattern of the target gene across different cancer types and to assess its connection with patient survival. Additionally, the expression levels of the target gene in PTC tumor tissues and adjacent healthy tissues will be verified using quantitative real-time PCR (RT-qPCR) with specifically designed primers. Survival analysis using fresh-frozen PTC tissue samples will be conducted to evaluate the capability of the target gene as a prognostic biomarker.
  • Results: A total of 1,978 genes with significant differential expression (|logFC| ≥ 2, FDR < 0.05) were found. The gene that codes for aldehyde oxidase 1 (AOX1) was chosen for additional study because of its significant downregulation (logFC = −2.71). Reactome analysis showed that AOX1 is linked to pathways related to the metabolism of water-soluble vitamins, cofactors, and the pharmacokinetic pathway of crizotinib. GO enrichment analysis suggested that AOX1 is involved in electron transport activities and has oxidoreductase functions. GEO Disease Perturbations analysis showed decreased AOX1 expression in idiopathic pulmonary fibrosis, idiopathic urticaria, and PTC. Additionally, pan-cancer analysis revealed modified AOX1 expression in breast, endometrial, ovarian, non-small cell lung (NSCLC), and prostate cancers.
  • Conclusion: Our results show that AOX1 is notably downregulated in PTC and could serve as a potential tumor-suppressive gene in this cancer. Considering the essential functions of water-soluble vitamin and cofactor metabolic pathways in energy metabolism, redox balance, and responses to oxidative stress, AOX1 might play a role in tumor development and metabolic reprogramming in PTC owing to its participation in these biological functions. Additionally, the oxidoreductase function of AOX1 and its involvement in electron transport indicate that lower AOX1 levels might be linked to a disturbance in cellular redox balance, thus establishing an environment conducive to PTC advancement. The persistent downregulation of AOX1 in various inflammatory and fibrotic conditions, such as PTC, indicates a possible involvement of this gene in common pathways associated with inflammation, cellular stress, and the remodeling of the tumor microenvironment. Thus, the recognition of AOX1 as a notably downregulated gene in PTC underscores its possible biological and clinical importance and calls for additional research as a diagnostic and prognostic biomarker.
  • Keywords: papillary thyroid carcinoma ; AOX1 gene ;RT- qPCR

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