Spinal Surgery Department, The Central Hospital of Lishui City.
Orthopaedics Department, Lishui City People's Hospital, Lishui.
Medicine (Baltimore). 2021 Mar 19;100(11):e24818. doi: 10.1097/MD.0000000000024818.
Osteosarcoma is a malignant tumor that develops from a mesenchymal cell line and is caused by gene-environment interactions. This study aimed to explore whether TIMP2/TIMP3 polymorphisms influenced the osteosarcoma risk.The expression of the TIMP2 and TIMP3 genes in osteosarcoma histiocytes was analyzed by immunohistochemistry. In this case-control study, which includes samples from 499 patients and 500 healthy controls, 10 single-nucleotide polymorphisms (SNPs) in TIMP2 and TIMP3 were selected. Furthermore, we used the Agena MassARRAY platform for genotyping. The statistical analysis was performed using χ2 test/Fisher exact test, and logistic regression analysis.The immunohistochemistry results showed that the expression of TIMP2 is obvious higher in osteosarcoma histiocytes than in the normal histiocytes. The association study indicated that the allele of rs2277698 and rs4789936 were protective SNPs reducing the risk of osteosarcoma (odds ratios > 1, P < .05) by the χ2 test. In the genetic model, logistic regression analyses revealed that the rs2277698 and rs4789936 were associated with decreasing the risk of osteosarcoma under the codominant model, dominant model, and log-additive model. Stratification analysis revealed that 2 SNPs (rs2277698 and rs4789936) were significantly associated with a reduced risk of osteosarcoma in allele and genetic model after stratification by gender or age (P < .05). In addition, the haplotype "Trs2277698Crs2009169Crs7342880" of TIMP2 was associated with decreasing the osteosarcoma risk. The "Ars9609634Trs11547635" of TIMP3 was associated with reducing the osteosarcoma risk.This finding shed new light on the high expression of TIMP2 polymorphisms may contribute to decreasing the osteosarcoma risk in Zhejiang populations.
骨肉瘤是一种来源于间充质细胞系的恶性肿瘤，是基因-环境相互作用的结果。本研究旨在探讨 TIMP2/TIMP3 多态性是否影响骨肉瘤的风险。采用免疫组织化学方法分析骨肉瘤组织细胞中 TIMP2 和 TIMP3 基因的表达。在这项包含 499 例患者和 500 例健康对照的病例对照研究中，选择了 TIMP2 和 TIMP3 中的 10 个单核苷酸多态性（SNP）。此外，我们使用 Agena MassARRAY 平台进行基因分型。采用 χ2 检验/ Fisher 精确检验和 logistic 回归分析进行统计学分析。免疫组织化学结果显示，骨肉瘤组织细胞中 TIMP2 的表达明显高于正常组织细胞。关联研究表明，rs2277698 和 rs4789936 等位基因是保护性 SNP，通过 χ2 检验降低骨肉瘤的发病风险（比值比>1，P<.05）。在遗传模型中，logistic 回归分析显示 rs2277698 和 rs4789936 与在共显性模型、显性模型和对数相加模型下降低骨肉瘤的发病风险相关。分层分析显示，在按性别或年龄分层后，2 个 SNP（rs2277698 和 rs4789936）在等位基因和遗传模型中与骨肉瘤发病风险降低显著相关（P<.05）。此外，TIMP2 的“Trs2277698Crs2009169Crs7342880”单体型与降低骨肉瘤风险相关。TIMP3 的“Ars9609634Trs11547635”与降低骨肉瘤风险相关。本研究结果提示 TIMP2 多态性的高表达可能有助于降低浙江人群骨肉瘤的发病风险。
