Abstract：
Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and reported. This meta-analysis aimed to assess the prognostic value of cytokines as osteosarcoma biomarkers. Databases including PubMed, Embase, and Cochrane Library were searched for studies on the prognostic value of cytokines in osteosarcoma. From the eligible studies, data on overall survival (OS), disease-free survival, and metastasis-free survival (MFS) were extracted. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. A total of 11 studies involving 755 patients were included in this analysis. High macrophage migration inhibitory factor (MIF) expression in tumors was significantly associated with shortened OS (HR = 2.01, 95% CI: 1.18-3.42, P = 0.010) and MFS (HR = 2.51, 95% CI: 1.47-4.01, P = 0.001). Elevated T cell immunoglobulin and mucin domain-3 (Tim-3) levels in serum correlated with increased risk of disease progression in patients with osteosarcoma (HR = 3.14, 95% CI: 2.88-3.03, P < 0.001). However, interleukin 6 (IL-6) and tumor necrosis factor were not substantially associated with osteosarcoma prognosis. Owing to a paucity of research, other relevant cytokines [interferon-α/β receptor, tissue factor, macrophage inhibitory cytokine 1 (MIC-1), and IL-23] could not be combined. In conclusion, MIF levels in tumors and Tim-3 levels in serum can be potential biomarkers of poor prognosis in osteosarcoma. To confirm this finding and implement these biomarkers into clinical applications, additional large-scale, high-quality studies are needed.
摘要：
骨肉瘤是儿童和青少年中最常见的原发性骨恶性肿瘤。细胞因子对骨肉瘤预后的影响已被研究和报道。这项荟萃分析旨在评估细胞因子作为骨肉瘤生物标志物的预后价值。包括PubMed在内的数据库,Embase,和Cochrane文库被搜索以研究细胞因子在骨肉瘤中的预后价值。从符合条件的研究中，总生存期(OS)数据，无病生存,提取无转移生存期(MFS)。计算集合风险比(HR)和95%置信区间(CI)。本分析共纳入11项研究，涉及755名患者。肿瘤中巨噬细胞移动抑制因子(MIF)的高表达与OS缩短(HR=2.01,95%CI:1.18~3.42,P=0.010)和MFS(HR=2.51,95%CI:1.47~4.01,P=0.001)显著相关。血清中T细胞免疫球蛋白和粘蛋白结构域3（Tim-3）水平升高与骨肉瘤患者疾病进展风险增加相关（HR=3.14，95％CI：2.88-3.03，P<0.001）。然而,白细胞介素6（IL-6）和肿瘤坏死因子与骨肉瘤的预后无关。由于缺乏研究，其他相关细胞因子[干扰素α/β受体，组织因子，巨噬细胞抑制细胞因子1（MIC-1），和IL-23]不能合并。总之,肿瘤中的MIF水平和血清中的Tim-3水平可能是骨肉瘤预后不良的潜在生物标志物。为了确认这一发现并将这些生物标志物应用于临床应用，额外的大规模，需要高质量的研究。
