Molecular detection of Epstein-Barr virus in paraffin-embedded tissue samples of patients suffering gastric cancer in Ahvaz, Iran: a case-control study
-
Mehdi Gharibzadeh
,
Shahram Jalilian
,
Manoochehr Makvandi
,
Seyed Saeid Seyedian
,
Azarakhsh Azaran
Abstract
Background and Objectives: Gastric cancer (GC) is the third most common cause of cancer-related mortality. Epstein-Barr virus (EBV) is associated with several human tumors. The present research was performed to investigate the prevalence of EBV-associated gastric cancer (EBVaGC) among Iranian patients.
Materials and Methods: Seventy cases of gastric cancer and 30 cases of gastric ulcer, all preserved in formalin-fixed paraffin-embedded (FFPE), were examined in a case-control study conducted between 2011 and 2018. The specimens underwent analysis to detect the presence of the EBV genome using a Nested-PCR method targeting EBNA1. Subsequently, samples testing positive for the EBNA1 underwent further testing for the presence of the EBER gene using PCR. Finally, Positive samples were subjected to sequencing.
Results: Five out of 70 cases (7%) were found to be positive for EBV based on EBNA1 testing, while all EBNA1 positive samples were negative for EBER. Notably, EBV was not detected in patients with gastric ulcer. The mean age of EBV-positive gastric carcinomas pateints was 64.5 years. Within this group, 60% were male and 40% were female. A higher prevalence of EBV association was observed in diffuse-type cases, with 60% (3 out of 24) testing positive, compared to intestinal-type cases where 40% (2 out of 46) were EBV-positive. Most cases of EBVaGC belonged to grade Ⅰ.
Conclusion: This research demonstrates a low prevalence of EBVaGC in Iran. Discrepancies in EBVaGC occurrence among countries could be attributed to epidemiological variables and dietary practices. A comprehensive studies will provide significant contributions to understanding of its etiology.
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2. Tavakoli A, Monavari SH, Solaymani Mohammadi F, Kiani SJ, Armat S, Farahmand M. Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis. BMC Cancer 2020; 20: 493.
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5. Naseem M, Barzi A, Brezden-Masley C, Puccini A, Berger MD, Tokunaga R, et al. Outlooks on Epstein-Barr virus associated gastric cancer. Cancer Treat Rev 2018; 66: 15-22.
6. Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK. Epstein–Barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: an update. Front Oncol 2018; 8: 211.
7. Majerciak V, Yang W, Zheng J, Zhu J, Zheng Z-M. A genome-wide Epstein-Barr virus polyadenylation map and its antisense RNA to EBNA. J Virol 2019; 93(2): e01593-18.
8. Buschle A, Hammerschmidt W. Epigenetic lifestyle of Epstein-Barr virus. Semin Immunopathol 2020; 42: 131-142.
9. Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer. Int J Oncol 2015; 46: 1421-1434.
10. Elyasi MM, Makvandi M, Ranjbari N, Latifi SM, Kaydani GA, Shamloo MBB. Prevalence of human polyomavirus BK virus in prostate cancer patients and benign prostatic Hyperplasia: A Cross-sectional study on prostate patients referred to Imam Khomeini hospital in Ahvaz between 2015 and 2017. Jundishapur J Microbiol 2021; 14(5): e115388.
11. Sadeghi F, Bokharaei‐Salim F, Salehi‐Vaziri M, Monavari SH, Alavian SM, Salimi S, et al. Associations between human TRIM22 gene expression and the response to combination therapy with Peg‐IFNα‐2a and ribavirin in Iranian patients with chronic hepatitis C. J Med Virol 2014; 86: 1499-1506.
12. Sambrook J, Russell DW (2001). Molecular Cloning: A laboratory manual. 3rd Edition, Vol. 1, cold Spring Harbor laboratory Press, New York.
13. Bojun L (2005). Expression of EBV genes in nasopharyngeal carcinoma. https://scholarbank.nus.edu.sg/handle/10635/17096
14. Makvandi M, Jalilian S, Faghihloo E, Khanizadeh S, Ramezani A, Bagheri S, et al. Prevalence of human papillomavirus and co-infection with Epstein-Barr virus in oral and oropharyngeal squamous cell carcinomas. Asian Pac J Cancer Prev 2022; 23: 3931-3937.
15. Lee J, Park M, Lee MH, Woo HJ, Kim H-W, Yang JY, et al. Development of EBV-encoded small RNA targeted PCR to classify EBV positive diffuse large B-cell lymphoma (DLBCL) of the elderly. Int J Clin Exp Pathol 2015; 8: 7859-7868.
16. Faghihloo E, Saremi MR, Mahabadi M, Akbari H, Saberfar E. Prevalence and characteristics of Epstein-Barr virus-associated gastric cancer in Iran. Arch Iran Med 2014; 17: 767-770.
17. Akiba S, Koriyama C, Herrera‐Goepfert R, Eizuru Y. Epstein‐Barr virus associated gastric carcinoma: Epidemiological and clinicopathological features. Cancer Sci 2008; 99: 195-201.
18. Faghihloo E, Saremi MR, Mahabadi M, Akbari H, Saberfar E. Prevalence and characteristics of Epstein-Barr virus-associated gastric cancer in Iran. Arch Iran Med 2014; 17: 767-770.
19. Leila Z, Arabzadeh SA, Afshar RM, Afshar AA, Mollaei HR. Detection of Epstein-Barr virus and cytomegalovirus in gastric cancers in Kerman, Iran. Asian Pac J Cancer Prev 2016; 17: 2423-2428.
20. Amoueian S, Attaranzadeh A, Gholamimoallem Z, Sadeghi M, Hashemi S-M, Allahyari A. Epstein–Barr virus infection in adult patients with gastric cancer in Northeast of Iran. Indian J Med Paediatr Oncol 2018; 39: 206-209.
21. Lee MA, Hong YS, Kang JH, Lee KS, You JY, Lee KY, et al. Detection of Epstein-Barr virus by PCR and expression of LMP1, p53, CD44 in gastric cancer. Korean J Intern Med 2004; 19: 43-47.
22. Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, et al. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal. World J Gastroenterol 2017; 23: 7292-7302.
23. Hirabayashi M, Georges D, Clifford GM, de Martel C. Estimating the global burden of Epstein-Barr virus–associated gastric cancer: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023; 21: 922-930. e21.
24. Abdirad A, Ghaderi-Sohi S, Shuyama K, Koriyama C, Nadimi-Barforoosh H, Emami S, et al. Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades. Diagn Pathol 2007; 2: 25.
25. Alipov G, Nakayama T, Nakashima M, Wen C-Y, Niino D, Kondo H, et al. Epstein-Barr virus-associated gastric carcinoma in Kazakhstan. World J Gastroenterol 2005; 11: 27-30.
26. Carrascal E, Koriyama C, Akiba S, Tamayo O, Itoh T, Eizuru Y, et al. Epstein-Barr virus-associated gastric carcinoma in Cali, Colombia. Oncol Rep 2003; 10: 1059-1062.
27. Karim N, Pallesen G. Epstein-Barr virus (EBV) and gastric carcinoma in Malaysian patients. Malays J Pathol 2003; 25: 45-47.
28. Wang Q, Liu G, Hu C. Molecular classification of gastric adenocarcinoma. Gastroenterology Res 2019; 12: 275-282.
29. Koriyama C, Akiba S, Corvalan A, Carrascal E, Itoh T, Herrera-Goepfert R, et al. Histology-specific gender, age and tumor-location distributions of Epstein-Barr virus-associated gastric carcinoma in Japan. Oncol Rep 2004; 12: 543-547.
30. Song H-J, Kim K-M. Pathology of epstein-barr virus-associated gastric carcinoma and its relationship to prognosis. Gut Liver 2011; 5: 143-148.
31. Re V, Brisotto G, Repetto O, De Zorzi M, Caggiari L, Zanussi S, et al. Overview of epstein–barr-virus-associated gastric cancer correlated with prognostic classification and development of therapeutic options. Int J Mol Sci 2020; 21: 9400.
32. Truong CD, Feng W, Li W, Khoury T, Li Q, Alrawi S, et al. Characteristics of Epstein-Barr virus-associated gastric cancer: a study of 235 cases at a comprehensive cancer center in USA. J Exp Clin Cancer Res 2009; 28: 14.
2. Tavakoli A, Monavari SH, Solaymani Mohammadi F, Kiani SJ, Armat S, Farahmand M. Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis. BMC Cancer 2020; 20: 493.
3. Kalniņa Z, Meistere I, Kikuste I, Tolmanis I, Zayakin P, Linē A. Emerging blood-based biomarkers for detection of gastric cancer. World J Gastroenterol 2015; 21: 11636-11653.
4. Wang F-H, Shen L, Li J, Zhou Z-W, Liang H, Zhang X-T, et al. The Chinese society of clinical oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer. Cancer Commun (Lond) 2019; 39: 10.
5. Naseem M, Barzi A, Brezden-Masley C, Puccini A, Berger MD, Tokunaga R, et al. Outlooks on Epstein-Barr virus associated gastric cancer. Cancer Treat Rev 2018; 66: 15-22.
6. Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK. Epstein–Barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: an update. Front Oncol 2018; 8: 211.
7. Majerciak V, Yang W, Zheng J, Zhu J, Zheng Z-M. A genome-wide Epstein-Barr virus polyadenylation map and its antisense RNA to EBNA. J Virol 2019; 93(2): e01593-18.
8. Buschle A, Hammerschmidt W. Epigenetic lifestyle of Epstein-Barr virus. Semin Immunopathol 2020; 42: 131-142.
9. Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer. Int J Oncol 2015; 46: 1421-1434.
10. Elyasi MM, Makvandi M, Ranjbari N, Latifi SM, Kaydani GA, Shamloo MBB. Prevalence of human polyomavirus BK virus in prostate cancer patients and benign prostatic Hyperplasia: A Cross-sectional study on prostate patients referred to Imam Khomeini hospital in Ahvaz between 2015 and 2017. Jundishapur J Microbiol 2021; 14(5): e115388.
11. Sadeghi F, Bokharaei‐Salim F, Salehi‐Vaziri M, Monavari SH, Alavian SM, Salimi S, et al. Associations between human TRIM22 gene expression and the response to combination therapy with Peg‐IFNα‐2a and ribavirin in Iranian patients with chronic hepatitis C. J Med Virol 2014; 86: 1499-1506.
12. Sambrook J, Russell DW (2001). Molecular Cloning: A laboratory manual. 3rd Edition, Vol. 1, cold Spring Harbor laboratory Press, New York.
13. Bojun L (2005). Expression of EBV genes in nasopharyngeal carcinoma. https://scholarbank.nus.edu.sg/handle/10635/17096
14. Makvandi M, Jalilian S, Faghihloo E, Khanizadeh S, Ramezani A, Bagheri S, et al. Prevalence of human papillomavirus and co-infection with Epstein-Barr virus in oral and oropharyngeal squamous cell carcinomas. Asian Pac J Cancer Prev 2022; 23: 3931-3937.
15. Lee J, Park M, Lee MH, Woo HJ, Kim H-W, Yang JY, et al. Development of EBV-encoded small RNA targeted PCR to classify EBV positive diffuse large B-cell lymphoma (DLBCL) of the elderly. Int J Clin Exp Pathol 2015; 8: 7859-7868.
16. Faghihloo E, Saremi MR, Mahabadi M, Akbari H, Saberfar E. Prevalence and characteristics of Epstein-Barr virus-associated gastric cancer in Iran. Arch Iran Med 2014; 17: 767-770.
17. Akiba S, Koriyama C, Herrera‐Goepfert R, Eizuru Y. Epstein‐Barr virus associated gastric carcinoma: Epidemiological and clinicopathological features. Cancer Sci 2008; 99: 195-201.
18. Faghihloo E, Saremi MR, Mahabadi M, Akbari H, Saberfar E. Prevalence and characteristics of Epstein-Barr virus-associated gastric cancer in Iran. Arch Iran Med 2014; 17: 767-770.
19. Leila Z, Arabzadeh SA, Afshar RM, Afshar AA, Mollaei HR. Detection of Epstein-Barr virus and cytomegalovirus in gastric cancers in Kerman, Iran. Asian Pac J Cancer Prev 2016; 17: 2423-2428.
20. Amoueian S, Attaranzadeh A, Gholamimoallem Z, Sadeghi M, Hashemi S-M, Allahyari A. Epstein–Barr virus infection in adult patients with gastric cancer in Northeast of Iran. Indian J Med Paediatr Oncol 2018; 39: 206-209.
21. Lee MA, Hong YS, Kang JH, Lee KS, You JY, Lee KY, et al. Detection of Epstein-Barr virus by PCR and expression of LMP1, p53, CD44 in gastric cancer. Korean J Intern Med 2004; 19: 43-47.
22. Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, et al. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal. World J Gastroenterol 2017; 23: 7292-7302.
23. Hirabayashi M, Georges D, Clifford GM, de Martel C. Estimating the global burden of Epstein-Barr virus–associated gastric cancer: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023; 21: 922-930. e21.
24. Abdirad A, Ghaderi-Sohi S, Shuyama K, Koriyama C, Nadimi-Barforoosh H, Emami S, et al. Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades. Diagn Pathol 2007; 2: 25.
25. Alipov G, Nakayama T, Nakashima M, Wen C-Y, Niino D, Kondo H, et al. Epstein-Barr virus-associated gastric carcinoma in Kazakhstan. World J Gastroenterol 2005; 11: 27-30.
26. Carrascal E, Koriyama C, Akiba S, Tamayo O, Itoh T, Eizuru Y, et al. Epstein-Barr virus-associated gastric carcinoma in Cali, Colombia. Oncol Rep 2003; 10: 1059-1062.
27. Karim N, Pallesen G. Epstein-Barr virus (EBV) and gastric carcinoma in Malaysian patients. Malays J Pathol 2003; 25: 45-47.
28. Wang Q, Liu G, Hu C. Molecular classification of gastric adenocarcinoma. Gastroenterology Res 2019; 12: 275-282.
29. Koriyama C, Akiba S, Corvalan A, Carrascal E, Itoh T, Herrera-Goepfert R, et al. Histology-specific gender, age and tumor-location distributions of Epstein-Barr virus-associated gastric carcinoma in Japan. Oncol Rep 2004; 12: 543-547.
30. Song H-J, Kim K-M. Pathology of epstein-barr virus-associated gastric carcinoma and its relationship to prognosis. Gut Liver 2011; 5: 143-148.
31. Re V, Brisotto G, Repetto O, De Zorzi M, Caggiari L, Zanussi S, et al. Overview of epstein–barr-virus-associated gastric cancer correlated with prognostic classification and development of therapeutic options. Int J Mol Sci 2020; 21: 9400.
32. Truong CD, Feng W, Li W, Khoury T, Li Q, Alrawi S, et al. Characteristics of Epstein-Barr virus-associated gastric cancer: a study of 235 cases at a comprehensive cancer center in USA. J Exp Clin Cancer Res 2009; 28: 14.
| Files | ||
| Issue | Vol 16 No 5 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v16i5.16805 | |
| Keywords | ||
| Gastric cancer; Gastric ulcer; Epstein-barr virus infection; Iran | ||
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How to Cite
1.
Gharibzadeh M, Jalilian S, Makvandi M, Seyedian SS, Azaran A. Molecular detection of Epstein-Barr virus in paraffin-embedded tissue samples of patients suffering gastric cancer in Ahvaz, Iran: a case-control study. Iran J Microbiol. 2024;16(5):689-697.
