Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas, Pulau Pinang, Malaysia.
Pathology. 2017 Dec;49(7):731-739. doi: 10.1016/j.pathol.2017.08.009. Epub 2017 Oct 23.
DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.
DNMT1 是已批准的抗癌药物（包括地西他滨）的靶点。然而，DNMT1 蛋白表达在 R-CHOP 治疗弥漫性大 B 细胞淋巴瘤（DLBCL）中的预后价值仍未得到探索。在这里，我们表明 DNMT1 在大多数 DLBCL 病例（n=209/230，90.9%）中表达，在生发中心 B 细胞样（GCB）-DLBCL 亚型中表达更高。低表达和阴性 DNMT1 表达（20%截断值，n=33/230，14.3%）预测总体生存率（OS；p<0.001）和无进展生存率（PFS；p<0.001）更差。尽管如此，在 209 例 DNMT1 阳性患者中，33%和 42%分别未能达到 5 年 OS 和 PFS，这表明 DNMT1 阳性患者的结局存在相当大的异质性。此外，DNMT1 在有丝分裂细胞中频繁表达，并与 Ki-67 或 BCL6 表达显著相关（r=0.60 或 0.44，分别；p<0.001）。我们证明了 DNMT1 可预测 DLBCL 患者的生存情况，并表明由于 DNMT1 与 Ki-67 显著相关，DNMT1 可能成为 DLBCL 的治疗靶点。
