Background Hepatitis B virus (HBV) infection (surface antigen positive, HBsAg+) has been linked to the increased risk and poor prognosis for B-cell lymphoma. Here, we aimed to explore clinically applicable prognostic index in HBV-associated follicular lymphoma (FL).
Methods Retrospective investigation was performed for clinical features from three clinical centers in China. We used the Human Methylation 850K BeadChip platform to detect DNA methylation signatures in HBsAg+ tumors occurring POD24 after bendamustine plus rituximab (BR) or cyclophosphamide, doxorubicin, vincristine and prednosine plus rituximab (R-CHOP) treatment.
Results HBsAg+ FL were featured with higher incidence of disease progression within 24 months (POD24) and poor survival, especially those with high HBV-DNA load (>10^5 copies/mL). Patients with HBsAg+ FL who received BR had relatively poor progression-free survival (PFS, P = 0.048) than those treated with R-CHOP (figures 1, 2). Among HBsAg+ tumors occurring POD24 after BR treatment, the signatures of methylated KMT2A, EP300-AS1, ARID1B and the majority of MHC I class molecular genes were detected (figures 3, 4). Besides, TNFRSF1A in epigenetic module played important role in negative regulation of disease progression after BR treatment, whereas LTA in module was involved in positive regulation. We proposed new scoring combined with HBV-related clinical parameters, treatment strategies, and FLIPI to define a high-risk group with worse outcomes than those defined by FLIPI (mean OS, 67.7 vs 69.8) (figure 5).
Conclusions HBsAg+ tumors occurring POD24 after BR treatment had some different methylation features from those after R-CHOP treatment. The combination of virus-related parameters with FLIPI could provide a better predictive model in FL.
Acknowledgements We appreciate all the patients participated. Sinotech Genomics Co., Ltd provides the technique support. The clinical data collection and partial sample provision are supported by the Harbin Medical University Cancer Hospital, the Tianjin Medical University Cancer Institute and Hospital, the Fourth Hospital of Hebei Medical University, the Shandong University Cancer Center, the First Affiliated Hospital of Harbin Medical University, and the Henan Cancer Hospital. The authors would like to thank all the reviewers who participated in the review.
Ethics Approval All study procedures were approved by the Institutional Review Boards (IRBs) of the Harbin Medical University Cancer Hospital, the Tianjin Medical University Cancer Institute and Hospital, the Fourth Hospital of Hebei Medical University, the Shandong University Cancer Center, the First Affiliated Hospital of Harbin Medical University, and the Henan Cancer Hospital. All participating patients provided written informed consent. This study was performed in accordance with the Declaration of Helsinki.
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