title: A high risk of osteosarcoma in individuals who are homozygous for the p.D104N in endostatin.
abstract: The D104N polymorphism (p.D104N) in endostatin has been previously identified in many types of cancer, and this polymorphism is believed to be a phenotypic modulator in some tumors. However, it is unknown whether endostatin p.D104N affects the risk and progression of osteosarcoma (OS). Here, we analyzed the p.D104N endostatin variant in 236 patients with OS and 418 healthy individuals. Similar frequencies of wild type and heterozygous p.104DN endostatin were observed in controls and OS patients. Interestingly, the frequency of the homozygous p.D104N (p.104NN) genotype was higher in OS patients group compared to control group, suggesting that individuals with p.104NN endostatin have a significantly increased risk for OS. In addition, OS patients with p.104NN endostatin had a shorter survival time and a higher rate of metastasis than OS patients with wild type endostatin. Animal experiments revealed that overexpression of p.104NN endostatin did not significantly inhibit OS lung metastasis. Interestingly, administration of endostatin dramatically inhibited OS lung metastasis in the p.104NN endostatin xenograft model. Together, these results suggest that p.104NN of endostatin is associated with the risk of OS and demonstrates predictive significance for clinical outcome in OS patients. In addition, endostatin therapy may be necessary for OS patients harboring p.104NN endostatin.
authors.affiliation: Departments of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Bi
authors.affiliation: Departments of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Dian-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Departments of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Song
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Pathology, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Song
authors.affiliation: Department of Pathology, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, FL 33647, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Departments of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Li
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Departments of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
mesh_terms: D043169:Endostatins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D043169:Endostatins