The Expression of mRNA LMP1 Epstein-Barr Virus from FFPE Tumour Biopsy: a Potential Biomarker of Nasopharyngeal Carcinoma Diagnosis

Daniel Joko Wahyono(1), Nur Signa Aini Gumilas(2), Hidayat Sulistyo(3),

DOI: https://doi.org/10.15294/biosaintifika.v9i2.9028


(1) Faculty of Biology, Universitas Jenderal Soedirman, Purwokerto, Indonesia
(2) Faculty of Medicine, Universitas Jenderal Soedirman, Purwokerto, Indonesia
(3) Faculty of Medicine, Universitas Jenderal Soedirman, Purwokerto, Indonesia

Abstract

Nasopharyngeal carcinoma (NPC) is a multifactorial disease that is endemic geographically in the world. Indonesian population has a highly incidence rate that is 6.2/100,000 people year. The pathogenesis of NPC is more directly reflected by carcinoma-specific viral transcriptional activity at the site of primary tumour. Epstein-Barr virus (EBV) infection in NPC is reflected by the expression of EBV latent and lytic gene. In fact, mRNA Latent Membrane Protein 1 (LMP1) EBV expression was an important latent infection biomarker. The aim of this study was to determine a potential use of relative expression of mRNA LMP1 EBV from formalin-fixed paraffin embedded (FFPE) tumour biopsy in NPC as a tumour biomarker. This reseach design was a cross sectional study. The samples were the archived specimens of FFPE tumour biopsy from NPC WHO-3 patient which were collected from untreated patients from 2014 in the Department of Pathology Anatomy, Prof. dr. Margono Soekarjo Hospital, Purwokerto. The expression of mRNA LMP1 EBV expression was determined by RT-PCR technique. The positivity of mRNA LMP1 EBV expression was 51.9%, indicating a moderate positivity. The result proved that the expression of mRNA LMP1 EBV from FFPE NPC WHO-3 tumour biopsy was a potential biomarker of NPC diagnosis. The molecular methods would improved the management of NPC, particularly in the histopathological diagnosis of NPC.

Keywords

mRNA LMP1 EBV expression; FFPE tumour biopsy; biomarker; NPC WHO-3; diagnosis

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References

Adham, M., Kurniawan, A. N., Muhtadi, A. I., Roezin, A., Hermani, B., Gondhowiardjo, S., & Middeldorp, J. M. (2012). Nasopharynngeal Carcinoma in Indonesia : Epidemiology, Incidence, Sign & Symptom at Presenation. Chinese Journal of Cancer, 31(4), 185-196.

Barnes, L., Eveson, J. W., Reichart, P., Sidransky, D. (2000). (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Lyon : IARC Press, 85-97.

Boos, H., Berger, R., Kuklik-Roos, C., Iftner, T., & Mueller-Lantzsch, N. (1987). Enhancement of Epstein-Barr virus membrane protein (LMP) expression by serum, TPA, or n-butyrate in latently infected Raji cells. Virol, 159(1), 161-65.

Brink, A. A., Oudejans, J. J., Jiwa, M., Walboomers, J. M., Meijer, C. J., & van den Brule, A. J. (1997). Multiprimed cDNA synthesis followed by PCR is the most suitable method for Epstein-Barr virus transcript analysis in small lymphoma biopsies. Molecular and cellular probes, 11(1), 39-47.

Chang, E. T., & Adami, H. O. (2006). The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiology and Prevention Biomarkers, 15(10), 1765-1777.

Chang, Y., Chang, S.S., Lee, H.H., Doong, S.L., Takada, K., Tsai, C.H. (2004). Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference. Journal of general virology, 85(6), 1371-1379.

Cho, W. C. S. (2007). Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Molecular cancer, 6(1).

Feng, P., Ren, E. C., Liu, D., Chan, S. H., & Hu, H. (2000). Expression of Epstein–Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis. Journal of General Virology, 81(10), 2417-2423.

Gouveia, G. R., Ferreira, S. C., Ferreira, J. E., Siqueira, S. A. C., & Pereira, J. (2014). Comparison of two methods of RNA extraction from formalin-fixed paraffin-embedded tissue specimens. BioMed research international, 2014.

Gulley, M. L. (2001). Molecular diagnosis of Epstein-Barr virus-related disease. The Journal of Molecular Diagnostics, 3(1), 1-10.

Hao, S. P., Tsang, N. M., Chang, K. P., & Ueng, S. H. (2004). Molecular diagnosis of nasopharyngeal carcinoma: detecting LMP-1 and EBNA by nasopharyngeal swab. Otolaryngology—Head and Neck Surgery, 131(5), 651-654.

Hirankarn, N., Kimkong, I., & Mutirangura, A. (2004). HLA‐E polymorphism in patients with nasopharyngeal carcinoma. HLA, 64(5), 588-592.

Kieff, E. & Rickinson, A. B. (2001). Epstein-Barr virus and Its Replication. In : Virology. 4th ed. Fields BN, Knipe DM, Howley PM, editors. Philadelphia : Lippincott-Raven, 2511-2573.

Kresno, S. B. (2011). Ilmu Dasar Onkologi. Edisi Kedua. Jakarta: Penerbit FKUI.

Martel-Renoir, D., Grunewald, V., Touitou, R., Schwaab, G., & Joab, I. (1995). Qualitative analysis of the expression of Epstein—Barr virus lytic genes in nasopharyngeal carcinoma biopsies. Journal of general virology, 76(6), 1401-1408.

Middeldorp, J. M., Brink, A. A., van den Brule, A. J., & Meijer, C. J. (2003). Pathogenic roles for Epstein–Barr virus (EBV) gene products in EBV-associated proliferative disorders. Critical reviews in oncology/hematology, 45(1), 1-36.

Munir, D. (2006). Beberapa Aspek Karsinoma Nasofaring pada Suku Batak di medan dan sekitarnya. J Med School USU, 39(3), 223-226.

Niedobitek, G. (2000). Epstein-Barr virus infection in the patogenesis of nasopharyngeal carcinoma. Molecular Pathology, 53(5), 248.

[OIE] Office international des Epizooties. (2005). Update on avian influenza viruses, including highly pathogenic H5N1 from poultry in live bird market in Hanoi, Vietnam in 2001. J Virol, 79: 4201- 4212.

Old, L. J., Boyse, E. A., Oettgen, H. F., De Harven, E., Geering, G., Williamson, B., & Clifford, P. (1966). Precipitating antibody in human serum to an antigen present in cultured Burkitt’s lymphoma cells. Proceedings of the National Academy of Sciences, 56(6), 1699-1704.

Payungporn, S., Phakdeewirot, P., Chu-tinimitkul, S., Theamboonlers, A., Keawcharoen, J., Oraveerakul, K., Amonsin, A., & Poovororawan, Y. (2004). Single-step multiplex reverse transcription-polymerase chain reaction (RT-PCR) for influenza A virus subtype H5N1 detection. Viral Immunol, 17(4), 588-593.

Rezeki, M., Parwati, I., Bethy., & Tjandrawati, A. (2014). Validitas Multiplex Real Time Polymerase Chain Reaction untuk Diagnosis Limfadenitis Tuberkulosis pada Spesimen Blok Parafin. MKB, 46(3), 162-167.

Roezin, A. (1999). Berbagai faktor penyebab dan predisposisi karsinoma nasofaring. Maj Kedokt Indon, 49(3), 85-88.

Soeripto. (1998). Epidemiology of nasopharyngeal carcinoma. Berita Kedokteran Masyarakat, XIII : 207-11.

Stevens, S. J., Verkuijlen, S. A., van den Brule, A. J., & Middeldorp, J. M. (2005). Comparison of quantitative competitive PCR with LC-based PCR for monitoring of Epstein-Barr virus (EBV) DNA load in clinical specimens. J Clin Microbiol, 40, 4105-13.

Stevens, S. J., Verkuijlen, S. A., Hariwiyanto, B., Paramita, D. K., Fachiroh, J., Adham, M., ... & Middeldorp, J. M. (2006). Noninvasive diganosis of nasopharyngeal carcinoma : nasopharyngeal brushing reveal high Epstein-Barr virus (EBV) DNA load and carcinoma-specific viral BARF1 mRNA. International journal of cancer, 119(3), 608-614.

Thompson, M. P. & Kurzrock, R. (2004). Epstein-Barr virus and cancer. Clin Cancer Res, 10(3), 803-821.

Verweij, F. J., Van Eijndhoven, M. A., Hopmans, E. S., Vendrig, T., Wurdinger, T., Cahir‐McFarland, E., ... & Middeldorp, J. M. (2011). LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF‐κB activation. The EMBO journal, 30(11), 2115-2129.

Wahyono, D. J., Musa, Z., Lisnawati, Suryandari, D. A., Hermani, B., & Soeharso, P. (2016). Host-patogen study : The relative expression of mRNA BRLF1 Epstein-Barr virus : a potensial use for biomarker of tumour progresivity &polymorphisms of TCRBC andTCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma. BMC Proceeding2016 : 7th Biannual International Symposium on Nasopharyngeal Carcinoma 2015, Yogyakarta, Indonesia.

Wibowo, A. A., Susanti R,. Umum, F., & Nugrahningsih, W. H. (2012). Isolasi dan identifikasi virus Avian Influenza subtype H5N1 di pertenakan tradisional, Kecamatan Gunungpati, Semarang. Biosaintifika: Journal of Biology & Biology Education, 4(2), 62-69.

Young, L. S. & Rickinson, A. B. (2004). Epstein-Barr virus : 40 years on. Nat Rev Cancer, 4(10), 757-68.

Yu, M. C. & Yuan, J. M. Epidemiology of nasopharyngeal carcinoma. (2002). Epidemiology of nasopharyngeal carcinoma. In Seminars in cancer biology (Vol. 12, No. 6, pp. 421-429). Academic Press.

Zur Hauzen, H. (1970). EBV DNA in biopsies of Burkitt tumors and anaplastic carcinomas of the nasopharynx. Nature, 228, 1956-1058.

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