MMP-11在膀胱癌中的表达及临床意义

Expression of MMP-11 in bladder cancer and its clinical significance

目的:探究MMP-11基因表达的在膀胱癌(BC)中的临床意义,并研究MMP-11推动BC发生、发展的机制。方法:从GEO数据库中下载BC基因表达数据集GSE13507,分析MMP-11在BC中的表达情况及MMP-11与BC的临床病理相关性和预后相关性;利用基因富集分析(GSEA)方法,分析MMP-11高表达样本的富集基因及MMP-11调控的相关通路。结果:MMP-11在BC中的表达水平明显高于其在正常膀胱组织中的表达水平(P=0.008);MMP-11高表达的BC患者在疾病进展(P=0.026)、T分期(P=0.001)、N分期(P<0.000 1)及分级(P<0.000 1)方面明显比MMP-11低表达组差;MMP-11高表达组BC患者的肿瘤特异性生存期明显差于MMP-11低表达组(P=0.000 2),MMP-11高表达组BC患者的总生存期亦有差于MMP-11低表达组的趋势(P=0.088 4);MMP-11高表达样本富集了与未折叠蛋白反应、精子形成、G2M检查点、MYC信号通路、E2F信号通路、MTORC1信号通路、有丝分裂纺锤体形成、血管生成、糖酵解、胆固醇平衡、PI3K/AKT/mTOR通路、炎症反应相关的基因集。结论:MMP-11在BC中高表达,且与BC的恶性程度和疾病进展相关,高表达MMP-11的BC患者临床预后更差。因此MMP-11或可作为潜在的判断BC患者预后的标志物和治疗BC的靶标。

Objective:To investigate the clinical relevance of MMP-11 expression in patients with bladder cancer(BC)and the corresponding mechanisms.Method:GEO dataset was collected and the corresponding expression profile and clinical information were analyzed.Gene set enrichment analysis(GSEA)was conducted to explore the associated gene sets regulated by MMP-11.Result:The expression of MMP-11 was upregulated in BC(P =0.008).MMP-11 expression was significantly associated with progression(P=0.026),T stage(P=0.001),N stage(P<0.000 1),grade(P<0.000 1).Higher expression of MMP-11 predicted poor specific survival in BC(P=0.000 2),and higher expression of MMP-11 tended to predict poor overall survival in BC(P=0.088 4).The results of GSEA indicated that MMP-11 regulated gene sets associated with unfolded protein response,spermatogenesis,G2 Mcheckpoint,MYC signaling pathway,E2 Ftargets,mTORC1 signaling pathway,mitotic spindle formation,angiogenesis,glycolysis,cholesterol homeostasis,PI3 K/AKT/mTOR signaling pathway,inflammatory response.Conclusion:MMP-11 was highly expressed in BC,correlated with worse clinicalpathological features and acted as a prognostic marker and target in the diagnosis and treatment of patients with BC.