Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma
Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma
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非霍奇金淋巴瘤中乙型肝炎病毒感染和病毒 DNA 整合的特征
DOI：
10.1002/ijc.33027
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发表时间：
2020-05-09
影响因子：
6.4
通讯作者：
Tu, Hong
中科院分区：
文献类型：
--
作者：
Li, Mengge;Shen, Yuling;Tu, Hong
据报道，B型肝炎病毒（HBV）感染与非霍奇金淋巴瘤（NHL）有关。然而，证据仅限于血清流行病学研究。缺乏证据表明HBV感染和整合在NHL细胞中。本文报道上海地区NHL患者血清HBsAg（OR：3.11，95%CI：2.20-4.41）和HBeAg（OR：3.99，95%CI：1.73-9.91）的阳性率显著增高。NHL组织中HBsAg、HBcAg和HBVDNA的阳性率分别为34.4%、45.2%和47.0%。此外，通过使用高通量病毒整合检测方法（HIVID），从50%（6/12）的HBV相关NHL组织中鉴定出整合的HBV DNA。从NHL组织中共分离出313个HBV整合位点，其中4个蛋白编码基因（FAT 2、SETX、ITGA 10和CD 63）的外显子被HBV DNA中断。7个HBV优先靶基因（ANKS 1B、HDAC 4、EGFLAM、MAN 1C 1、XKR 6、ZBTB 38和CCDC 91）在NHL中的表达水平显著改变，表明这些基因在NHL发展中的潜在作用。综上所述，HBV整合是NHL中的常见现象。这一发现为HBV感染和NHL之间的机制联系开辟了新的研究方向。
Hepatitis B virus (HBV) infection has been reported to be associated with non-Hodgkin lymphoma (NHL). However, the evidence is limited to the seroepidemiological study. There is a lack of evidence showing the HBV infection and integration in NHL cells. Here, we reported that in the Shanghai area, the positive rates of serum HBsAg (OR: 3.11; 95% CI: 2.20-4.41) and HBeAg (OR: 3.99; 95% CI: 1.73-9.91) were significantly higher in patients with NHL. HBsAg, HBcAg and HBV DNA were detected in 34.4%, 45.2% and 47.0% of the NHL tissues, respectively. Furthermore, by using a high-throughput viral integration detection approach (HIVID), integrated HBV DNA was identified from 50% (6/12) HBV-related NHL tissues. There were a total of 313 HBV integration sites isolated from the NHL tissues, among which four protein-coding genes (FAT2, SETX, ITGA10 and CD63) were interrupted by HBV DNA in their exons. Seven HBV preferential target genes (ANKS1B, HDAC4, EGFLAM, MAN1C1, XKR6, ZBTB38 and CCDC91) showed significantly altered expression levels in NHL, suggesting a potential role of these genes in NHL development. Taken together, HBV integration is a common phenomenon in NHL. This finding opens up a new direction of research into the mechanistic link between HBV infection and NHL.