Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-beta1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-beta1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment.


METHODS
A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA.


RESULTS
A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 +/- 637 copies/mL; n = 51) following treatment (57 +/- 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 +/- 37 pg/mL; n = 51) and following treatment (58 +/- 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages.


CONCLUSIONS
We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome.
Tan
Eng-lai
EL
School of Pharmacy and Health Sciences, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. tanenglai@netscape.net
Selvaratnam
G
G
Kananathan
R
R
Sam
Choon-kook
CK
D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006133:Growth Substances / Q000097:blood*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D019089:Stem Cell Factor / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D019562:Viral Load
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C041788:Epstein-Barr viral capsid antigen; D006133:Growth Substances; D007070:Immunoglobulin A; D015850:Interleukin-6; D019089:Stem Cell Factor; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10