Bioinformatic Analysis of Genes Involved In The Pathogenesis Of Ameloblastoma And Human Tooth Germ

Main Article Content

Sangamithra.S
Abilasha Ramasubramanian
Vijayashree Priyadharsini J
Pratibha Ramani

Keywords

Analysis, Germ, potential, human

Abstract

Background: Pathogenesis of most odontogenic tumors is not well established. It is important to identify various genetic deregulations and molecular alterations. Common signaling pathways between ameloblastoma and human tooth germ is yet to be well established. This study aimed to investigate, through bioinformatic analysis, the possible genes involved in the pathogenesis of ameloblastoma (AM) and human tooth germ.
Aim: To analyze the genes commonly expressed in human tooth germ and ameloblastoma for better understanding the molecular pathogenesis of ameloblastoma.
Materials and methods: This is an in-silico study. GeneCards database was used for this study. The database was used to identify important genes expressed in the formation of human tooth germ and ameloblastoma. The potential candidate genes were then mapped using an online program STRING (version 11.5). This identified the interaction of networks between the protein-coding genes. The genes which showed a high degree of confidence were included and their direct and indirect interactions were evaluated. Each gene interaction was scored to produce an overall association score. The genes which displayed the highest WNL score were mentioned as leader genes.
Results: GeneCards and STRING analysis showed a final count of 10 genes that were commonly expressed in ameloblastoma and human tooth germ were included. These were : IGF1 , STAT1 , TLR2 , BRAF , IGF2 , ERK2 , ERK1 , NFkappaB , MEK2 and MEK1. From the WNL analysis, ameloblastoma, the highest WNL values were identified in genes BRAF V600E, MAPK, STAT1 and NFKappaB, The most relevant WNL values for human tooth germ are IGF1, IGF2, TLR1, TLR2 , STAT1 and NKKappaB1.


Conclusion: STAT 1 and NFKappaB together help in tumor cell proliferation and cell survival. Numerous targeted therapies have been produced against these genes. Further in vitro molecular analysis such as microarray are needed for proper application of these therapies.

Abstract 348 | PDF Downloads 200

References

1. Adebayo, Ezekiel Taiwo, Sunday Olusegun Ajike, and Emmanuel Oladepo Adekeye. 2002. “Odontogenic Tumours in Children and Adolescents: A Study of 78 Nigerian Cases.” Journal of Cranio-Maxillo-Facial Surgery: Official Publication of the European Association for Cranio-Maxillo-Facial Surgery 30 (5): 267–72.
2. Alexander, Aurelian Jovita, Pratibha Ramani, Herald J. Sherlin, and S. Gheena. 2019. “Quantitative Analysis of Copper Levels in Areca Nut Plantation Area - A Role in Increasing Prevalence of Oral Submucous Fibrosis: An Study.” Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research 30 (2): 261–66.
3. Arumugam, Paramasivam, Rinku George, and Vijayashree Priyadharsini Jayaseelan. 2021. “Aberrations of m6A Regulators Are Associated with Tumorigenesis and Metastasis in Head and Neck Squamous Cell Carcinoma.” Archives of Oral Biology 122 (February): 105030.
4. Au-Yeung, Nancy, Roli Mandhana, and Curt M. Horvath. 2013. “Transcriptional Regulation by STAT1 and STAT2 in the Interferon JAK-STAT Pathway.” JAK-STAT 2 (3): e23931.
5. Awadalkreem, Fadia, and Omer Abdoun. 2020. “Enucleation and Surgical Stent as a Treatment Strategy for a Large Unicystic Ameloblastoma: Case Report and Review of Literature.” International Journal of Surgery Case Reports 77 (November): 371–77.
6. Chatra, Laxmikanth, Sham Kishor Kanneppady, Santosh B. Sakri, S. Nanditha, and K. Prashanth Shenoy. 2011. “Unicystic Ameloblastoma in a Young Female: A Case Report and Review of Literature.” World Journal of Dentistry. https://doi.org/10.5005/jp-journals-10015-1094.
7. Darnell, J. E., Jr, I. M. Kerr, and G. R. Stark. 1994. “Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins.” Science 264 (5164): 1415–21.
8. Deschamps, Matthieu, Guillaume Laval, Maud Fagny, Yuval Itan, Laurent Abel, Jean-Laurent Casanova, Etienne Patin, and Lluis Quintana-Murci. 2016. “Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes.” American Journal of Human Genetics 98 (1): 5–21.
9. Elumalai, Perumal, Devaraj Ezhilarasan, and Thangavelu Lakshmi. 2022. “Targeting Head and Neck Cancer Epigenetics with CRISPR-dCas9: An Emerging Therapeutic Approach.” Oral Oncology 127 (April): 105801.
10. Frobel, Philipp. n.d. “STAT1 AND STAT3 MUTATIONS AS TARGET FOR GENE THERAPY.” https://doi.org/10.26226/morressier.57bc1757d462b80290b4cff4.
11. Gomes, Carolina Cavalieri, Alessandra Pires Duarte, Marina Gonçalves Diniz, and Ricardo Santiago Gomez. 2010. “Review Article: Current Concepts of Ameloblastoma Pathogenesis.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 39 (8): 585–91.
12. Guo, Tingting, Ci Zhang, and Jian Zhou. n.d. “Unicystic Ameloblastoma in a 9-Year-Old Child Treated with a Combination of Conservative Surgery and Orthodontic Treatment: A Case Report.” https://doi.org/10.22541/au.163628239.96423110/v1.
13. Han, Yulong, Douglas W. Leaman, Diane Watling, Neil C. Rogers, Bernd Groner, Ian M. Kerr, William I. Wood, and George R. Stark. 1996. “Participation of JAK and STAT Proteins in Growth Hormone-Induced Signaling.” Journal
of Biological Chemistry. https://doi.org/10.1074/jbc.271.10.5947.
14. Horvath, C. M., G. R. Stark, I. M. Kerr, and J. E. Darnell. 1996. “Interactions between STAT and Non-STAT Proteins in the Interferon-Stimulated Gene Factor 3 Transcription Complex.” Molecular and Cellular Biology. https://doi.org/10.1128/mcb.16.12.6957.
15. Jayaraman, Selvaraj, Jayanthi Pazhani, Vishnu PriyaVeeraraghavan, A. Thirumal Raj, Dinesh Babu Somasundaram, and Shankargouda Patil. 2022. “PCNA and Ki67: Prognostic Proliferation Markers for Oral Cancer.” Oral Oncology 130 (July): 105943.
16. Jenkins, Brendan John. 2014. “Transcriptional Regulation of Pattern Recognition Receptors by JAK/STAT Signaling, and the Implications for Disease Pathogenesis.” Journal of Interferon & Cytokine Research. https://doi.org/10.1089/jir.2014.0081.
17. Kim, Jwayoung, Eunkyung Nam, and Sukho Yoon. 2017. “Conservative Management (marsupialization) of Unicystic Ameloblastoma: Literature Review and a Case Report.” Maxillofacial Plastic and Reconstructive Surgery. https://doi.org/10.1186/s40902-017-0134-0.
18. Lin, Sheng-Chieh, Yi-Chu Liao, Po-Ming Chen, Ya-Yu Yang, Yi-Hsiang Wang, Shiao-Lin Tung, Chi-Mu Chuang, et al. 2022. “Periostin Promotes Ovarian Cancer Metastasis by Enhancing M2 Macrophages and Cancer-Associated Fibroblasts via Integrin-Mediated NF-κB and TGF-β2 Signaling.” Journal of Biomedical Science 29 (1): 109.
19. Mirzaei, Sepideh, Mahshid Deldar Abad Paskeh, Maliheh Entezari, Seyed Hesamoddin Bidooki, Vahideh Javadian Ghaleh, Shamin Rezaei, Elahe Sadat Hejazi, et al. 2022. “siRNA and Targeted Delivery Systems in Breast Cancer Therapy.” Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, December. https://doi.org/10.1007/s12094-022-03043-y.
20. Mithra, and Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University. 2021. “Genetic Association of Bcl2 (rs2279115) Gene Polymorphism with Susceptibility to Oral Cancer - A Case Control Study in South Indian Population.” International Journal of Dentistry and Oral Science, July, 3431–34.
21. Mony, Ullas, and Vishnu Priya Veeraraghavan. 2022. “‘Rules’ to the Genetic Progression of Tumours Deciphered: Is It Time to Think Differently in Treating Oral Cancer Patients?” Oral Oncology 134 (November): 106111.
22. Morgan, Peter R. 2011. “Odontogenic Tumors: A Review.” Periodontology 2000 57 (1): 160–76.
23. Mosqueda-Taylor, Adalberto. 2008. “New Findings and Controversies in Odontogenic Tumors.” Medicina Oral, Patologia Oral Y Cirugia Bucal 13 (9): E555–58.
24. Ogasa, M. 2003. “Gastrin Activates Nuclear Factor kappaB (NFkappaB) through a Protein Kinase C Dependent Pathway Involving NFkappaB Inducing Kinase, Inhibitor kappaB (IkappaB) Kinase, and Tumour Necrosis Factor Receptor Associated Factor 6 (TRAF6) in MKN-28 Cells Transfected with Gastrin Receptor.” Gut. https://doi.org/10.1136/gut.52.6.813.
25. Orlando, B., N. Bragazzi, and C. Nicolini. 2013. “Bioinformatics and Systems Biology Analysis of Genes Network Involved in OLP (Oral Lichen Planus) Pathogenesis.” Archives of Oral Biology 58 (6): 664–73.
26. Pandiar, Deepak, Pratibha Ramani, P. M. Shameena, Reshma Poothakulath Krishnan, and K. Monica. 2022. “Adenoid Ameloblastoma: A Neglected Variant of Ameloblastoma or a Separate Entity?” Oral Oncology 125 (February): 105681.
27. Paramasivam, Arumugam. 2022. “Plasma Circulating Tumor DNA as a Molecular Marker for Oral Cancer.” Oral Oncology 130 (July): 105926.
28. Peng, Hong, Ting Ye, Lei Deng, Xiaofang Yang, Zheng Jiang, and Jinjun Guo. 2022. “Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis.” Canadian Journal of Gastroenterology & Hepatology 2022 (December): 8996203.
29. Philipsen, Hans P., and Peter A. Reichart. 2002. “Revision of the 1992-Edition of the WHO Histological Typing of Odontogenic Tumours. A Suggestion.” Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 31 (5): 253–58.
30. Pradeep, and Associate Professor, Department of Oral And Maxillofacial Surgery, Saveetha Dental college & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University. 2021. “Unicystic Ameloblastoma: Case Reports and Review of Literature Pradeep D.” International Journal of Dentistry and Oral Science, July, 3412–15.
31. Pradeep, and Senior Lecturer, Department of Conservative Dentistry and Endodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University. 2021. “Unicystic Mural Ameloblastoma: An Case Report and Review of Litrature.” International Journal of Dentistry and Oral Science, July, 3534–37.
32. Ramani, Pratibha, Reshma Poothakulath Krishnan, Deepak Pandiar, Aklesha Behera, and Abilasha Ramasubramanian. 2022. “Squamous Odontogenic Tumor like Proliferations in Dentigerous Cyst- a Great Mimicker.” Oral Oncology 125 (February): 105699.
33. Ramani, Pratibha, Reshma Poothakulath Krishnan, Deepak Pandiar, and Snega Thamilselvan. 2022. “A Rare Combined Motley Variety of Odontogenic Tumors - Hybrid Lesion or a New Entity?” Oral Oncology 124 (January): 105521.
34. Ramani, Pratibha, Deepak Pandiar, S. Gheena, and Reshma Poothakulath Krishnan. 2022. “Archegonous Cystic Odontoma: A Recently Described yet an under-Recognized Odontogenic Pathology.” Oral Oncology 127 (April): 105820.
35. Ramesh, Sindhu, and Professor, Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and technical Sciences, Saveetha University, Chennai, India. 2021. “Evaluation of Interleukin 6, Interleukin 8, TNF Alpha as Biomarkers for Pulpitis - in Vivo Study.” International Journal of Dentistry and Oral Science, February, 1655–60.
36. Rizzitelli, Alexandra, Nicolas R. Smoll, Michael P. Chae, Warren M. Rozen, and David J. Hunter-Smith. 2015. “Incidence and Overall Survival of Malignant Ameloblastoma.” PLOS ONE. https://doi.org/10.1371/journal.pone.0117789.
37. Sarode, Sachin C., Shailesh Gondivkar, Gargi S. Sarode, Amol Gadbail, and Monal Yuwanati. 2021. “Hybrid Oral Potentially Malignant Disorder: A Neglected Fact in Oral Submucous Fibrosis.” Oral Oncology 121 (October): 105390.
38. Sasikumar, P. K., Sheeja S. Varghese, Thanga Kumaran, and Sakthi Saranya Devi. 2020. “Meta-Analysis of Risk Association between Interleukin-17A Gene Polymorphism and Chronic Periodontitis.” Contemporary Clinical Dentistry 11 (1): 3–9.
39. Schindler, C., and J. E. Darnell. 1995. “TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway.” Annual Review of Biochemistry. https://doi.org/10.1146/annurev.bi.64.070195.003201.
40. Shen, Ziyi, Shengxiong Pu, Xing Cao, Ming Tang, Shenglin Wang, Dazhang Bai, and Guohui Jiang. 2022. “Bioinformatics and Network Pharmacology Analysis of Drug Targets and Mechanisms Related to the Comorbidity of Epilepsy and Migraine.” Epilepsy Research 189 (December): 107066.
41. Siar, Chong Huat, Shin Hin Lau, and Kok Han Ng. 2012. “Ameloblastoma of the Jaws: A Retrospective Analysis of 340 Cases in a Malaysian Population.” Journal of Oral and Maxillofacial Surgery. https://doi.org/10.1016/j.joms.2011.02.039.
42. Silva, Yuri Slusarenko da, Yuri Slusarenko da Silva, Natalia Aguiar Tartaroti, Daniel Isaac Sendyk, Maria Cristina Zindel Deboni, and Maria da Graça Naclério-Homem. 2018. “Is Conservative Surgery a Better Choice for the Solid/multicystic Ameloblastoma than Radical Surgery Regarding Recurrence? A Systematic Review.” Oral and Maxillofacial Surgery. https://doi.org/10.1007/s10006-018-0715-9.
43. Sivakumar, N., Anjali Narwal, Deepak Pandiar, Anju Devi, Rahul Anand, Deepty Bansal, and Mala Kamboj. 2022. “Diagnostic Utility of p63/p40 in the Histologic Differentiation of Salivary Gland Tumors: A Systematic Review.” Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 133 (2): 189–98.
44. Sorriento, Daniela, Jessica Gambardella, and Guido Iaccarino. 2021. “Cancer, NFkappaB, and Oxidative Stress-Dependent Phenotypes.” Cancer. https://doi.org/10.1016/b978-0-12-819547-5.00016-x.
45. “TNFR1-Induced NFkappaB Signaling Pathway.” n.d. Reactome. https://doi.org/10.3180/r-hsa-5357956.2.
46. Troiano, Giuseppe, Mario Dioguardi, Armando Cocco, Luigi Laino, Gabriele Cervino, Marco Cicciu, Domenico Ciavarella, and Lorenzo Lo Muzio. 2017. “Conservative vs Radical Approach
for the Treatment of Solid/Multicystic Ameloblastoma: A Systematic Review and Meta-Analysis of the Last Decade.” Oral Health & Preventive Dentistry 15 (5): 421–26.
47. Trosman, Samuel J., and Paul R. Krakovitz. 2015. “Pediatric Maxillary and Mandibular Tumors.” Otolaryngologic Clinics of North America 48 (1): 101–19.
48. Wagner, Michael A., and M. A. Q. Siddiqui. 2012. “The JAK-STAT Pathway in Hypertrophic Stress Signaling and Genomic Stress Response.” JAK-STAT. https://doi.org/10.4161/jkst.20702.
49. Yanar, Sevinc, Murat Kasap, Aylin Kanli, Gurler Akpinar, and Mehmet Sarihan. 2022. “Proteomics Analysis of Meclofenamic Acid-Treated Small Cell Lung Carcinoma Cells Revealed Changes in Cellular Energy Metabolism for Cancer Cell Survival.” Journal of Biochemical and Molecular Toxicology, December, e23289.
50. Yang, Ling, Yu-Xin Chen, Ying-Ying Li, Xiao-Juan Liu, Yong-Mei Jiang, and Jia Mai. 2022. “Systematic Analysis of Expression Profiles and Prognostic Significance for MMDS-Related Iron-Sulfur Proteins in Renal Clear Cell Carcinoma.” Scientific Reports 12 (1): 19637.
51. Yang, Yao-Cheng, Jun-Jie Wang, Yun Huang, Wei-Xin Cai, and Qian Tao. 2021. “Development and Validation of a Prognostic Nomogram for Postoperative Recurrence-Free Survival of Ameloblastoma.” Cancer Management and Research 13 (June): 4403–16.
52. Zhang, Zhao, Ye Peng, Jingyi Dang, Xincheng Liu, Dongze Zhu, Yushen Zhang, Yubo Shi, and Hongbin Fan. 2022. “Identification of Key Biomarkers Related to Epithelial-Mesenchymal Transition and Immune Infiltration in Ameloblastoma Using Integrated Bioinformatics Analysis.” Oral Diseases, February. https://doi.org/10.1111/odi.14173.

Most read articles by the same author(s)

1 2 3 > >>