Meng Jialin, Wang Shuo, Shen Xufeng, Bai Zhengming, Niu Qingsong, Ma Dongyue, Xu Yuchen, Liang Chaozhao
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China; Anhui Province PKD Center, Hefei, Anhui, China.
The First Clinical Collage of Anhui Medical University, Hefei, Anhui, China.
Pathol Res Pract. 2018 Dec;214(12):1966-1973. doi: 10.1016/j.prp.2018.09.011. Epub 2018 Sep 13.
Matrix metalloproteinases 9 (MMP-9) is a zinc-dependent gelatinase, which could decrease the expression of extracellular matrix proteins and influence the metastatic behavior of tumors. In order to draw a comprehensive and precise result about the relationship of MMP-9 and urinary cancers, we presented the current meta-analysis.
We searched the PubMed, EMbase, Web of Science, CBM, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until August 2018. Quality assessment was conducted using the Newcastle-Ottawa Scale. All the meta-analysis was conducted with Stata version 12.0 software to assess the strength of the association. Linkage disequilibrium (LD) analyses of gene polymorphisms and in-silico analysis of MMP-9 expression were also conducted to illustrate the relationship.
17 case-control studies comprise of more than 6154 cases and 6330 controls were enrolled and analyzed. After analyzed, we found that there is no significant association between rs3918241, rs2250889, rs17576 and rs17577 of MMP-9 and urinary cancers. LD analysis uncovered a significant LD between rs3918241 and rs17577 in CEU, CHB&CHS, ESN, and JPT populations (CEU: r = 1.0; CHB&CHS: r = 1.0; ESN: r = 0.74; JPT: r = 0.77), as well as a remarkable LD between rs17576 and rs2250889 in CHB&CHS and JPT populations (CHB&CHS: r = 0.81; JPT: r = 0.82). Furthermore, in-silico results indicated that the expression of MMP-9 in cancer tissue was higher than that in normal tissue in prostate cancer (Transcripts Per Kilobase Million (TPM) = 7.14 vs. 1.36, P < 0.001), bladder cancer (TPM = 14.2 vs. 2.47, P < 0.001), kidney renal clear cell carcinoma (TPM = 7.43 vs. 1.61, P < 0.001), kidney renal papillary cell carcinoma (TPM = 5.52 vs. 1.74, P = 0.002).
rs3918241, rs2250889, rs17576 and rs17577 polymorphisms of MMP-9 are not associated with altered risk of urinary cancer. More studies with large sample size focused on the combined effect of two or more polymorphisms of MMP-9 are necessary in the future.
基质金属蛋白酶9（MMP-9）是一种锌依赖性明胶酶，它可降低细胞外基质蛋白的表达并影响肿瘤的转移行为。为了得出关于MMP-9与泌尿系统癌症关系的全面且精确的结果，我们进行了当前的荟萃分析。
我们检索了PubMed、EMbase、Web of Science、中国生物医学文献数据库（CBM）、中国知网（CNKI）和万方数据库，还手动再次检索了参考文献，涵盖截至2018年8月发表的所有论文。使用纽卡斯尔-渥太华量表进行质量评估。所有荟萃分析均使用Stata 12.0软件进行，以评估关联强度。还进行了基因多态性的连锁不平衡（LD）分析以及MMP-9表达的电子分析以阐明这种关系。
纳入并分析了17项病例对照研究，包括6154例以上病例和6330例对照。分析后，我们发现MMP-9的rs3918241、rs2250889、rs17576和rs17577与泌尿系统癌症之间无显著关联。LD分析发现，在CEU、CHB&CHS、ESN和JPT人群中，rs3918241与rs17577之间存在显著的LD（CEU：r = 1.0；CHB&CHS：r = 1.0；ESN：r = 0.74；JPT：r = 0.77），在CHB&CHS和JPT人群中，rs17576与rs2250889之间也存在显著的LD（CHB&CHS：r = 0.81；JPT：r = 0.82）。此外，电子分析结果表明，在前列腺癌（每百万碱基转录本数（TPM）= 7.14对1.36，P < 0.001）、膀胱癌（TPM = 14.2对2.47，P < 0.001）、肾透明细胞癌（TPM = 7.43对1.61，P < 0.001）、肾乳头状细胞癌（TPM = 5.52对1.74，P = 0.002）中，癌组织中MMP-9的表达高于正常组织。
MMP-9的rs3918241、rs2250889、rs17576和rs17577多态性与泌尿系统癌症风险改变无关。未来有必要开展更多大样本研究，聚焦MMP-9两个或更多多态性的联合效应。
