Differential expression of viral agents in lymphoma tissues of patients with ABC diffuse large B-cell lymphoma from high and low endemic infectious disease regions

Abstract

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed lymphomas worldwide. Environmental factors, such as viruses and bacteria, may contribute to cancer development through chronic inflammation and the integration of oncogenes, and have previously been indicated in cervical cancer, hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In the present study, the presence of microbial agents was analyzed in the lymphoma tissue of patients with activated B-cell like (ABC) DLBCL. The present study compared two groups of patients from geographically varied regions that possess a difference in the prevalence of viral and other microbial agents. The patient populations were from Sweden (a low endemic infectious disease region) and Egypt (a high endemic infectious disease region). A differential expression of several viruses in lymphoma tissues was noted when comparing Swedish and Egyptian patients. JC polyomavirus (JCV) was detected in Swedish and Egyptian patients and, uniquely, the complete hepatitis B virus (HBV) genome was detected only in Egyptian lymphoma patients. None of these viruses were detected in control lymph tissues from Sweden or Egypt. In total, 38% of the Egyptian patients were found to have HBV surface antigens (HBsAgs) in their serum; however, HBsAgs were not found in any of the Swedish patients. The percentage of serum HBsAgs in Egyptian patients with ABC DLBCL was significantly increased compared with the general Egyptian population (P<0.05). The present study may support a notion that viral agents, including JCV and HBV, may be involved in the tumorigenesis of DLBCL in regions of high infectious disease.

Keywords: gene array; hepatitis B virus; lymphoma and Hodgkin disease; molecular genetics; virus.

Figure 1.

Bar graph showing detected viruses from the microbial detection array. Log-odd scores are indicated on the y-axis. Red bars indicate Egyptian patients, blue bars indicate Swedish patients, purple bars indicate Egyptian control samples and green bars indicate Swedish control samples. Each bar indicates the detection of a virus, including the complete genome, strain or isolate. Strains and isolate numbers are indicated. Eg, Egyptian; Swe, Swedish.

Figure 2.

Bar graph summarizing log-odd scores for each patient or control group. Statistical analysis (Student's t-test) was performed and indicates statistical difference between the groups. No significant difference was shown between the controls sample groups. EG, Egyptian; SWE, swedish; C, control; Pat, patient.

Figure 3.

Box plot showing relative expression of (A) STAT3 and (B) miRNA in EG (+HBV) and EG (−HBV) patients and SV (−HBV) patients. Statistical analysis (analysis of variance) shows a significant difference between SV and EG patients. There were no statistical differences between EG (+HBV) and EG (−HBV) patients. EG, Egyptian, SV, Swedish; HBV, hepatitis B virus; STAT3, signal transducers and activators of transcription 3; miRNA, micro RNA.