Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur Autonomous Region, 830011, China.
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). doi: 10.1073/pnas.2016653118.
Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.
骨肉瘤是最常见的骨恶性肿瘤，主要影响青少年和年轻人。基于动物研究，半个多世纪前提出了骨肉瘤的病毒病因，但尚未发现人类骨肉瘤与病毒有关。中国新疆的维吾尔族人群中卡波西肉瘤相关疱疹病毒（KSHV）感染的流行率异常高，骨肉瘤的发病率也很高。在本研究中，我们探讨了 KSHV 感染与骨肉瘤发生的可能关联。我们的血清流行病学研究表明，维吾尔族骨肉瘤患者的 KSHV 流行率明显高于普通维吾尔族人群（OR，10.23；95%CI，4.25，18.89）。大多数骨肉瘤肿瘤细胞中均检测到 KSHV DNA 基因组和病毒潜伏核抗原 LANA。基因表达谱分析表明，KSHV 阳性骨肉瘤代表一种独特的骨肉瘤亚型，病毒基因激活的信号通路对骨肉瘤的发生很重要。我们的结论是，KSHV 感染是骨肉瘤的一个危险因素，并且 KSHV 与一些骨肉瘤有关，代表了一种新确定的与病毒相关的地方性癌症。
