title: Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma.
abstract: Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow-up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues (P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients.
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Shoulei
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Xiuxin
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Luling
authors.initials: L
authors.lastname: Shan
authors.affiliation: School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.
authors.forename: Biying
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Tianyang
authors.initials: T
authors.lastname: Mu
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. sxiong@mdanderson.org.
authors.forename: Shunbin
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. wangguowendr@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000601:surgery*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Chemokine (C-X-C-motif) receptor 4 (CXCR4); Matrix metalloproteinase 9 (MMP9); Osteosarcoma; Pulmonary metastasis