MMP9蛋白与甲状腺恶性肿瘤关系的Meta分析

Meta-Analysis of the Relationship between MMP9 Protein and Thyroid Cancer

摘要: 目的：探究MMP9蛋白在良性甲状腺结节与甲状腺恶性肿瘤的表达差异。方法：通过检索2020年12月31日之前PubMed、Web of Science、CNKI和万方数据库关于MMP9蛋白水平与甲状腺恶性肿瘤关系的病例对照研究。根据相应标准选择文献并提取相关的数据，采用纽卡斯尔–渥太华量表评价其方法学质量，提取的资料通过Stata12.0软件进行统计学分析，I2检验评价文章的异质性。结果：共纳入10篇符合要求的文献，其中包括554名诊断为甲状腺恶性肿瘤患者和337名良性甲状腺结节患者。甲状腺恶性肿瘤患者组织中MMP9蛋白水平明显高于良性甲状腺结节组，差异有统计学意义(OR = 9.80, 95% CI: 5.77~16.62, P < 0.05)。根据不同临床特征将甲状腺恶性肿瘤分为多个亚组进行Meta分析，结果显示MMP9的高表达与更大的肿瘤直径(OR = 3.37, 95% CI: 1.36~8.34, P < 0.05)，存在包膜侵犯(OR = 13.95, 95% CI: 4.13~47.09)，淋巴结转移(OR = 6.05, 95% CI: 3.28~11.15, P < 0.05)以及更高的TNM分期(OR = 5.03, 95% CI: 2.40~10.56, P < 0.05)密切相关。结论：MMP9蛋白在甲状腺恶性肿瘤中高表达，且与肿瘤直径大小、包膜侵犯、淋巴结转移、临床分期密切相关，有望成为甲状腺癌的一个新的治疗靶点。

Abstract: Objective: To investigate the difference of MMP9 protein expression in benign thyroid nodules and thyroid cancer. Methods: Case-control studies on the relationship between MMP9 protein levels and thyroid cancer by searching PubMed, Web of Science, CNKI and Wanfang databases before December 31, 2020. The literature was selected and relevant data were extracted according to the inclusion and exclusion criteria, and the methodological quality was evaluated using the Newcastle-Ottawa scale, and the extracted data were statistically analyzed by Stata 12.0 software, and the I2 test was used to evaluate the heterogeneity of the articles. Results: A total of 10 eligible articles, including 554 patients diagnosed with thyroid cancer and 337 patients with benign thyroid nodules were included. MMP9 protein levels were significantly higher in the samples from patients with thyroid cancer than in the group with benign thyroid nodules, with a statistically significant difference (OR = 9.80, 95% CI: 5.77~16.62, P < 0.05). Meta-analysis by dividing thyroid cancer into multiple subgroups by different clinical features showed that high expression of MMP9 was associated with larger tumor diameter (OR = 3.37, 95% CI: 1.36~8.34, P < 0.05), the presence of envelope invasion (OR = 13.95, 95% CI: 4.13~47.09), lymph node metastasis (OR = 6.05, 95% CI: 3.28~11.15, P < 0.05) and higher TNM stage (OR = 5.03, 95% CI: 2.40~10.56, P < 0.05) were closely associated. Conclusion: MMP9 protein is highly expressed in thyroid cancer tissues, closely correlated with tumor diameter size, envelope invasion, lymph node metastasis, and clinical stage, and is expected to be a new therapeutic target for thyroid cancer.