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Evaluation of Methylation and Changes in the Transcriptomics and Proteomics of the Grhl3, Phlda3, and in Patients With Head and Neck Squamous Cell Carcinoma Publisher



Shakoori A1 ; Azarian M2, 3 ; Hosseinpour Aghaei M4 ; Maddahi M5 ; Aghazadeh K6 ; Tabari A7 ; Farmani S8 ; Azani A9, 10 ; Moghadam Fard A11 ; Mokhtari Z12 ; Derakhshan A13 ; Idani A14 ; Lotfi M15 ; Zohourian Shahzadi S16 Show All Authors
Authors
  1. Shakoori A1
  2. Azarian M2, 3
  3. Hosseinpour Aghaei M4
  4. Maddahi M5
  5. Aghazadeh K6
  6. Tabari A7
  7. Farmani S8
  8. Azani A9, 10
  9. Moghadam Fard A11
  10. Mokhtari Z12
  11. Derakhshan A13
  12. Idani A14
  13. Lotfi M15
  14. Zohourian Shahzadi S16
  15. Siahbani S17
  16. Motamedi S18
  17. Saffarzadeh N9, 19
Show Affiliations
Authors Affiliations
  1. 1. Medical Genetic Ward, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Radiology, Charite Universitatsmedizin Berlin, Berlin, 10117, Germany
  3. 3. Department of Bioanalytical Ecotoxicology, UFZ Helmholtz Centre for Environmental Research, Leipzig, Germany
  4. 4. Shiraz University of Medical Science, Shiraz, Iran
  5. 5. Faculty of Dentistry, Yeditepe University, Istanbul, Turkey
  6. 6. Head and Neck Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Otolaryngology-Head and Neck Surgery, Otorhinolaryngology Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Genetics Group, Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
  9. 9. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  11. 11. Universal Scientific Education and Research Network (USERN), Tehran, Iran
  12. 12. Otorhinolaryngology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  13. 13. Genia Medical Genetics Laboratory, Tehran, Iran
  14. 14. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  15. 15. Mashhad Branch Islamic Azad University, Mashhad, Iran
  16. 16. Erfan Hospital, Iran University of Medical Sciences, Bakhshayesh, Iran
  17. 17. Molecular Pathology and Cytogenetic Ward, Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  18. 18. School of Public Health, Loma Linda University, Loma Linda, CA, United States
  19. 19. Genia Medical Genetics Laboratory, Department of Nephrology, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran

Source: Indian Journal of Otolaryngology and Head and Neck Surgery Published:2025


Abstract

Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy in the world. High mortality and severe complications are critical features of head and neck cancer. Changes in intracellular signaling pathways are a general tumor formation and progression mechanism. Due to the objectivity that the PI3K pathway plays a critical role in HNSCC. the negative regulators involved in this pathway such as GRHL3, PHLDA3, which have been reported to reduce their expression in malignancies, can achieve significant results in the detection, prognosis, and targeted treatment of HNSCC if changes in transcriptome, proteome, and methylation levels of these genes are observed. Method: 45 fresh head and neck cancer cells and 45 control samples were collected. Protein expression was also studied using Western blot. Additionally, promoter methylation was investigated using the qMSP method to observe changes in the regulatory regions. Results: The results indicate a significant decrease in GRHL3 expression and a significant increase in PHLDA3 expression. Notably, these expression changes were not confirmed at the protein level. Additionally, methylation analysis revealed hypermethylation of the promoter region in GRHL3 and hypomethylation in PHLDA3. Conclusion: This study is the first to examine the genes GRHL3 and PHLDA3 at the transcriptome, proteome, and promoter methylation levels. Based on the results, we hope that further studies will confirm the potential of GRHL3 and PHLDA3 as prognostic biomarkers. © Association of Otolaryngologists of India 2024.
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