Abstract 6019: Characteristics and impactof DNA methylationon prognosis in hepatitis B virus-related follicular lymphoma
Authors: Ma Jianli , Deng Yuwei , Zhang Huilai , Zhang Xiaosan , Liu Lihong , Wang Xianhuo , Song Hongtao , Zhang Zirong , Liu Caili , Zhang Qingyuan , Yu Jinming 
Published: April 2023

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 discover distinctive potential factors to influence the prognosis in HBV-associated follicular lymphoma (FL). Retrospective investigation from multiple clinical centers showed that patients with HBsAg+ FL were featured with a higher incidence of disease progression within 24 months (POD24, P=0.031), shorter progression-free survival (PFS, P = 0.004) and overall survival (OS, P = 0.039). The patients with high HBV-DNA load (&gt;10^5 copies/mL) had worse PFS (P &lt;0.001) and OS (P = 0.007). Methylation detection identified that POD24 in HBsAg+ FL were contributed by pro-tumoral methylated KMT2A, EP300-AS1, and ARID1B. The majority of MHC I class molecular retained hypermethylated status with silencing expression to promote immune escape and progression in HBsAg+ FL. Hypermethylated TNFRSF1A significantly contributed to prevent the POD24 of HBsAg+ FL, whereas hypermethylated LTA promoted progression. Regarding the unsatisfactory prognosis guidance based on FLIPI in patients with HBsAg+ FL, we proposed new scoring combined with HBV-related clinical parameters, contributed gene methylation and FLIPI to define a high-risk group with worse prognosis than FLIPI in our study (mean OS, 67.7 vs 69.8). It exhibited good performances in internal cohort and external validation cohort from other three clinical centers. Taken together, chronic HBV infection may affect methylation of the immune-related genes to promote progression in FL. The combination of clinical features and genes methylation with FLIPI could provide a better prognostic model for HBV-related FL.

Univariable and multivariable Cox regression analysis with respect to progression-free survival of c Univariate analysis Multivariate analysis HR 95%CI P value HR 95%CI P value Age(&gt;60 vs ≤60) 1.457 0.963-2.205 0.073* 1.608 1.037-2.493 0.034 Sex(male vs female) 0.876 0.578-1.325 0.529 Grade(3A va 1-2) 1.315 0.847-2.042 0.221 Ann Arbor stage(III/IV vs I/II) 0.852 0.526-1.379 0.513 Number of extranodal sites≥5 0.732 0.483-1.110 0.141 B symptoms 1.679 1.028-2.741 0.036* 2.023 1.142-3.584 0.016 BM involvement 0.690 0.383-1.244 0.215 High FLIPI risk 3.081 1.740-5.454 &lt;0.001* 1.972 1.023-3.803 0.043 Elevated LDH level 1.317 0.829-2.092 0.242 Serum albumin &lt;3.5 g/dL 2.633 1.315-5.270 0.004* 1.465 0.649-3.309 0.358 ALC &lt;1000/μL 1.581 0.641-3.898 0.316 HBsAg positivity 1.850 1.209-2.833 0.004* 1.184 0.705-1.991 0.523 HBeAg positivity 1.668 0.768-3.623 High HBV-DNA load(&gt;10^5 copies/mL) 4.110 2.360-7.160 &lt;0.001* 3.774 1.958-7.278 &lt;0.001 Treatment (BR vs R-CHOP) 1.261 0.752-2.113 0.379

Citation Format: Jianli Ma, Yuwei Deng, Huilai Zhang, Xiaosan Zhang, Lihong Liu, Xianhuo Wang, Hongtao Song, Zirong Zhang, Caili Liu, Qingyuan Zhang, Jinming Yu. Characteristics and impactof DNA methylationon prognosis in hepatitis B virus-related follicular lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6019.