1887

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Volume 97, Issue 1

Serological and viraemic status of human cytomegalovirus infection in patients with colorectal cancer is not correlated with viral replication and transcription in tumours Free

Abstract

Colorectal cancer (CRC) is amongst the leading causes of cancer-related mortality worldwide. Emerging evidence suggests that human cytomegalovirus (HCMV) exists in the tumour tissue of CRC and is associated with disease outcome. To study whether tumoral HCMV is related to viral reactivation in blood, tumour specimens and pre- and post-operative blood samples from CRC patients were collected prospectively. PCR and quantitative PCR were performed to detect HCMV DNA. HCMV IgG and IgM antibodies were measured using a microparticle enzyme immunoassay. Transcription of a spliced HCMV gene transcript was analysed by quantitative reverse transcription PCR. HCMV was detected in 42.2 % (35/83) of the tumour samples, with a low median viral load (30.08, range 2.33–5704 copies per 500 ng genomic DNA). The vast majority (80/81, 98.8 %) of the CRC patients were seropositive for HCMV IgG. HCMV DNA was positive in 11.3 % (22/194) of the pre-operative and 8.9 % (15/168) of the post-operative blood samples. However, presence of HCMV and its viral load in tumours were not associated with the detection or viral loads in blood samples. About 26.67 % (8/30) of the HCMV-positive tumours with available RNA had detectable viral transcripts, whilst none of the blood samples were positive for viral RNA ( < 0.0001). Therefore, presence of HCMV in tumours does not correlate with the serological or viraemic status of CRC patients. Active viral gene transcription occurred in the tumour but not in the blood of CRC patients. HCMV reactivation in CRC patients is possibly due to virus–cancer interactions in the CRC tumour microenvironment.

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© 2015 The Authors
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2016-01-01
2024-04-26
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References

  1. Blaheta R. A., Beecken W. D., Engl T., Jonas D., Oppermann E., Hundemer M., Doerr H. W., Scholz M., Cinatl J. Jr 2004; Human cytomegalovirus infection of tumor cells downregulates NCAM (CD56): a novel mechanism for virus-induced tumor invasiveness. Neoplasia 6:323–331 [View Article][PubMed]
     [Google Scholar]
  2. Caposio P., Orloff S. L., Streblow D. N. 2011; The role of cytomegalovirus in angiogenesis. Virus Res 157:204–211 [View Article][PubMed]
     [Google Scholar]
  3. Chemaly R. F., Torres H. A., Hachem R. Y., Nogueras G. M., Aguilera E. A., Younes A., Luna M. A., Rodriguez G., Tarrand J. J., Raad I. I. 2005; Cytomegalovirus pneumonia in patients with lymphoma. Cancer 104:1213–1220 [View Article][PubMed]
     [Google Scholar]
  4. Chen H. P., Jiang J. K., Chen C. Y., Chou T. Y., Chen Y. C., Chang Y. T., Lin S. F., Chan C. H., Yang C. Y., other authors. 2012; Human cytomegalovirus preferentially infects the neoplastic epithelium of colorectal cancer: a quantitative and histological analysis. J Clin Virol 54:240–244 [View Article][PubMed]
     [Google Scholar]
  5. Chen H. P., Jiang J. K., Lai P. Y., Chen C. Y., Chou T. Y., Chen Y. C., Chan C. H., Lin S. F., Yang C. Y., other authors. 2014; Tumoral presence of human cytomegalovirus is associated with shorter disease-free survival in elderly patients with colorectal cancer and higher levels of intratumoral interleukin-17. Clin Microbiol Infect 20:664–671 [View Article][PubMed]
     [Google Scholar]
  6. Cobbs C. S. 2011; Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis. Herpesviridae 2:10 [View Article][PubMed]
     [Google Scholar]
  7. Dal Monte P., Pignatelli S., Mach M., Landini M. P. 2001; The product of human cytomegalovirus UL73 is a new polymorphic structural glycoprotein (gpUL73). J Hum Virol 4:26–34[PubMed]
     [Google Scholar]
  8. Dimberg J., Hong T. T., Skarstedt M., Löfgren S., Zar N., Matussek A. 2013; Detection of cytomegalovirus DNA in colorectal tissue from Swedish and Vietnamese patients with colorectal cancer. Anticancer Res 33:4947–4950[PubMed]
     [Google Scholar]
  9. Evans C., Dalgleish A. G., Kumar D. 2006; Review article: immune suppression and colorectal cancer. Aliment Pharmacol Ther 24:1163–1177 [View Article][PubMed]
     [Google Scholar]
  10. Fisher R. A. 2009; Cytomegalovirus infection and disease in the new era of immunosuppression following solid organ transplantation. Transpl Infect Dis 11:195–202 [View Article][PubMed]
     [Google Scholar]
  11. Galon J., Costes A., Sanchez-Cabo F., Kirilovsky A., Mlecnik B., Lagorce-Pagès C., Tosolini M., Camus M., Berger A., other authors. 2006; Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964 [View Article][PubMed]
     [Google Scholar]
  12. Gandhi M. K., Khanna R. 2004; Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 4:725–738 [View Article][PubMed]
     [Google Scholar]
  13. Geder K. M., Lausch R., O'Neill F., Rapp F. 1976; Oncogenic transformation of human embryo lung cells by human cytomegalovirus. Science 192:1134–1137 [View Article][PubMed]
     [Google Scholar]
  14. Geder L., Laychock A. M., Gorodecki J., Rapp F. 1978; Alterations in biological properties of different lines of cytomegalorivus-transformed human embryo lung cells following in vitro cultivation. IARC Sci Publ 24:(Part 2)591–601[PubMed]
     [Google Scholar]
  15. Hahn G., Jores R., Mocarski E. S. 1998; Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci U S A 95:3937–3942 [View Article][PubMed]
     [Google Scholar]
  16. Han X. Y. 2007; Epidemiologic analysis of reactivated cytomegalovirus antigenemia in patients with cancer. J Clin Microbiol 45:1126–1132 [View Article][PubMed]
     [Google Scholar]
  17. Harkins L., Volk A. L., Samanta M., Mikolaenko I., Britt W. J., Bland K. I., Cobbs C. S. 2002; Specific localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 360:1557–1563 [View Article][PubMed]
     [Google Scholar]
  18. Huang E. S., Roche J. K. 1978; Cytomegalovirus D.N.A. and adenocarcinoma of the colon: evidence for latent viral infection. Lancet 311:957–960 [View Article][PubMed]
     [Google Scholar]
  19. Ives D. V. 1997; Cytomegalovirus disease in AIDS. AIDS 11:1791–1797 [View Article][PubMed]
     [Google Scholar]
  20. Mach M., Kropff B., Dal Monte P., Britt W. 2000; Complex formation by human cytomegalovirus glycoproteins M (gpUL100) and N (gpUL73). J Virol 74:11881–11892 [View Article][PubMed]
     [Google Scholar]
  21. Michaelis M., Doerr H. W., Cinatl J. Jr 2009; Oncomodulation by human cytomegalovirus: evidence becomes stronger. Med Microbiol Immunol (Berl) 198:79–81 [View Article][PubMed]
     [Google Scholar]
  22. Rahbar A., Peredo I., Solberg N. W., Taher C., Dzabic M., Xu X., Skarman P., Fornara O., Tammik C., other authors. 2015; Discordant humoral and cellular immune responses to Cytomegalovirus (CMV) in glioblastoma patients whose tumors are positive for CMV. OncoImmunology 4:e982391 [View Article][PubMed]
     [Google Scholar]
  23. Reeves M., Sinclair J. 2008; Aspects of human cytomegalovirus latency and reactivation. Curr Top Microbiol Immunol 325:297–313[PubMed]
     [Google Scholar]
  24. Saga K., Fukui T., Kato Y., Komeda T., Nakase H., Watanabe N., Nishio A., Chiba T. 2007; Localized cytomegalovirus reactivation after radiotherapy for high-grade gastric lymphoma. Gastrointest Endosc 65:545–547 [View Article][PubMed]
     [Google Scholar]
  25. Shen Y., Zhu H., Shenk T. 1997; Human cytomagalovirus IE1 and IE2 proteins are mutagenic and mediate hit-and-run oncogenic transformation in cooperation with the adenovirus E1A proteins. Proc Natl Acad Sci U S A 94:3341–3345 [View Article][PubMed]
     [Google Scholar]
  26. Sinclair J., Sissons P. 2006; Latency and reactivation of human cytomegalovirus. J Gen Virol 87:1763–1779 [View Article][PubMed]
     [Google Scholar]
  27. Söderberg-Nauclér C., Rahbar A., Stragliotto G. 2013; Survival in patients with glioblastoma receiving valganciclovir. N Engl J Med 369:985–986 [View Article][PubMed]
     [Google Scholar]
  28. Stragliotto G., Rahbar A., Solberg N. W., Lilja A., Taher C., Orrego A., Bjurman B., Tammik C., Skarman P., other authors. 2013; Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133:1204–1213 [View Article][PubMed]
     [Google Scholar]
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Serological and viraemic status of human cytomegalovirus infection in patients with colorectal cancer is not correlated with viral replication and transcription in tumours
J. Gen. Virol. 97, 152 (2016); https://doi.org/10.1099/jgv.0.000315
/content/journal/jgv/10.1099/jgv.0.000315
/content/journal/jgv/10.1099/jgv.0.000315
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