- Volume 15 Issue 20
DOI QR Code
Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma
- Khor, Goot Heah (Centre of Preclinical Science Studies, Faculty of Medicine, Universiti Teknologi MARA) ;
- Froemming, Gabrielle Ruth Anisah (Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA) ;
- Zain, Rosnah Binti (Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya) ;
- Abraham, Mannil Thomas (Tengku Ampuan Rahimah Hospital, Department of Oral and Maxillofacial Surgery, Ministry of Health Malaysia) ;
- Thong, Kwai Lin (Laboratory of Biomedical Science and Molecular Microbiology, UMBIO Cluster, Institute of Graduate Studies, University of Malaya)
- Published : 2014.11.06
Background: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis. Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status. Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.
Microarray;oral squamous cell carcinoma;promoter hypermethylation;MSPCR
- Bibikova M, Barnes B, Tsan C, et al (2011). High density DNA methylation array with single CpG site resolution. Genomics, 98, 288-95. https://doi.org/10.1016/j.ygeno.2011.07.007
- Aryee MJ, Liu W, Engelmann JC, et al (2013). DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases. Sci Transl Med, 5, 169ra110.
- Bibikova M, Yeakley, JM, Chudin E, et al (2004). Gene expression profiles in formalin-fixed, paraffin-embedded tissues obtained with a novel assay for microarray analysis. Clin Chem, 50, 2384-6. https://doi.org/10.1373/clinchem.2004.037432
- Bibikova M, Lin ZW, Zhou, L.X, et al (2006). High-throughput DNA methylation profiling using universal bead arrays. Genome Res, 16, 383-93. https://doi.org/10.1101/gr.4410706
- Cheng Y, Yan Z, Liu Y, et al (2014). Analysis of DNA methylation patterns associated with the gastric cancer genome. Oncol Lett, 7, 1021-6.
- Cottrell S, Laird PW (2003). Sensitive detection of DNA methylation. Ann N Y Acad Sci, 983, 120-30. https://doi.org/10.1111/j.1749-6632.2003.tb05967.x
- Herman JG, Graff JR, Myohanen SBDN, et al (1996). Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Nat Acad Sci USA, 93, 9821-6. https://doi.org/10.1073/pnas.93.18.9821
- Jiang Q, Yu YC, Ding XJ, Luo Y, Ruan H (2014). Bioinformatics analysis reveals significant genes and pathways to target for oral squamous cell carcinoma. Asian Pac J Cancer Prev, 15, 2273-8. https://doi.org/10.7314/APJCP.2014.15.5.2273
- Herman JG, Baylin SB (2003). Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med, 349, 2042-54. https://doi.org/10.1056/NEJMra023075
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA: A Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Jha, AK, Nikbakht M, Jain V,et al (2012). Promoter hypermethylation of p73 and p53 genes in cervical cancer patients among north Indian population. Mol Biol Rep, 39, 9145-57. https://doi.org/10.1007/s11033-012-1787-5
- Jones PA (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet, 12, 484-92.
- Kang GH, Lee S, Cho NY, et al (2007). DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis. Lab Invest, 88, 161-70.
- Khor GH, Froemming GRA, Zain RB, et al (2013). DNA Methylation Profiling Revealed Promoter Hypermethylationinduced Silencing of p16, DDAH2 and DUSP1 in Primary oral squamous cell carcinoma. Int J Med Sci, 10, 1727-39. https://doi.org/10.7150/ijms.6884
- Killian JK, Walker RL, Bilke S, et al (2012). Genome-wide methylation profiling in archival formalin-fixed paraffinembedded tissue samples. Methods Mol Biol, 823, 107-18. https://doi.org/10.1007/978-1-60327-216-2_8
- Kim JC, Kim, TW (2010). Promoter methylation of specific genes is associated with the phenotype and progression of colorectal adenocarcinomas. Ann Surg Oncol, 17, 1767-76. https://doi.org/10.1245/s10434-009-0901-y
- Liu Y, Liu CX, Wu ZT, Ge L, Zhou HM (2013). Mining proteins associated with oral squamous cell carcinoma in complex networks. Asian Pac J Cancer Prev, 14, 4621-5. https://doi.org/10.7314/APJCP.2013.14.8.4621
- O'Sullivan E, Goggins M (2013). DNA methylation analysis in human cancer.pancreatic cancer (pp. 131-156): Springer.
- Moore MA, Ariyaratne Y, Badar F, et al (2009). Cancer epidemiology in South Asia - past, present and future. Asian Pac J Cancer Prev, 11, 49-66.
- Nazmul-Hossain ANM, Patel KJ, Rhodus NL, et al (2008). Microarrays: applications in dental research. Oral Dis, 14, 25-9.
- Noushmehr H, Weisenberger DJ, Diefes K, et al (2010). Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell, 17, 510-22. https://doi.org/10.1016/j.ccr.2010.03.017
- Oster B, Thorsen K, Lamy P, et al (2011). Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas. Int J Cancer, 129, 2855-66. https://doi.org/10.1002/ijc.25951
- Patel KR, Valaria BN, Begum R, et al (2013). Association between p53 variants and oral cancer susceptibility in population from Gujarat, West India. Asian Pac J Cancer Prev, 14, 1093-100. https://doi.org/10.7314/APJCP.2013.14.2.1093
- Scully C (2011). Oral cancer aetiopathogenesis; past, present and future aspects. Med Oral Patol Oral Cir Bucal, 306-11. https://doi.org/10.4317/medoral.16.e306
- Shaw R (2006). The epigenetics of oral cancer. Int J Oral Maxillofac Surg, 35, 101-8. https://doi.org/10.1016/j.ijom.2005.06.014
- Supic G, Kozomara R, Brankovic-Magic M, et al (2009). Gene hypermethylation in tumor tissue of advanced oral squamous cell carcinoma patients. Oral Oncol, 45, 1051-7. https://doi.org/10.1016/j.oraloncology.2009.07.007
- Towle R, Truong D, Hogg K, et al (2013). Global analysis of DNA methylation changes during progression of oral cancer. Oral Oncol, 49, 1033-42. https://doi.org/10.1016/j.oraloncology.2013.08.005
- Warnakulasuriya S (2009). Global epidemiology of oral and oropharyngeal cancer. Oral Oncol, 45, 309-16. https://doi.org/10.1016/j.oraloncology.2008.06.002
- Weber M, Davies JJ, Wittig D, et al (2005). Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet, 37, 853-62. https://doi.org/10.1038/ng1598
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- Genome-wide haplotype association analysis identifies SERPINB9, SERPINE2, GAK, and HSP90B1 as novel risk genes for oral squamous cell carcinoma vol.37, pp.2, 2016, https://doi.org/10.1007/s13277-015-3965-2