Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin.
Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin.
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DOI：
10.18632/oncotarget.4677
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发表时间：
2015-09-22
期刊：
影响因子：
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通讯作者：
Zhu J
中科院分区：
文献类型：
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作者：
Deng L;Song Y;Young KH;Hu S;Ding N;Song W;Li X;Shi Y;Huang H;Liu W;Zheng W;Wang X;Xie Y;Lin N;Tu M;Ping L;Ying Z;Zhang C;Sun Y;Zhu J
虽然乙型肝炎病毒（HBV）感染与弥漫性大B细胞淋巴瘤（DLBCL）之间的流行病学关联已经确立，但除了这一流行病学证据之外，我们知之甚少。我们研究了587例DLBCL患者的HBV感染状况、临床病理特征和HBV表面抗原（HBsAg）阳性患者的免疫球蛋白可变区。81例（81/587,13.8%）患者hbsag阳性。与hbsag阴性DLBCL相比，hbsag阳性DLBCL表现出更年轻的中位发病年龄（45岁vs 55岁），更频繁地累及脾脏或腹膜后淋巴结（分别为40.7% vs. 16.0%和61.7% vs. 31.0%，均p < 0.001），更晚期的疾病（III/IV期：76.5% vs. 59.5%, p = 0.003），以及更差的结局（2年总生存率：47% vs. 70%, p < 0.001）。在HBsAg阳性的DLBCL患者中，几乎所有（45/ 47,96%）重链和轻链互补决定区3的氨基酸序列与HBsAg特异性抗体具有高度的同源性，大部分（45/ 50,90%）IgHV和IgLV基因发生突变。我们得出结论，在hbv流行的中国，13.8%的DLBCL病例与hbv相关，并表现出独特的临床特征和不良结局。此外，我们的研究强烈提示HBV相关的DLBCL可能来自HBV抗原选择的B细胞。
While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.