Matrix Metalloproteinase 11 is a Potential Biomarker in Bladder Cancer Diagnosis and Prognosis
Matrix Metalloproteinase 11 is a Potential Biomarker in Bladder Cancer Diagnosis and Prognosis
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DOI：
10.2147/ott.s243452
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Li, Sheng
中科院分区：
文献类型：
--
作者：
Chen, Chen;Liu, Xiaoping;Li, Sheng
目的：膀胱癌是全世界癌症死亡的主要原因之一，一半的患者在诊断时已处于晚期，治疗效果不佳。因此，迫切需要开发用于膀胱癌诊断和预后的新生物标志物。材料和方法：采用生物信息学和基因本体（GO）分析来筛选TCGA BLCA队列中高度上调和分泌性肿瘤标志物。使用组织微阵列中的 IHC 和癌细胞培养基中的 ELISA 来验证膀胱癌中推定生物标志物的表达。使用亚硫酸氢盐测序来检测推定基因启动子中的 DNA 甲基化状态。 结果：在本研究中，通过 TCGA 膀胱癌队列的荟萃分析，首次将 MMP11 确定为膀胱癌中差异最大的表达基因 (DEG) 之一。 MMP11 的强烈上调在膀胱癌患者和细胞系的蛋白质水平上得到证实。机制研究表明，MMP11 启动子低甲基化，而非基因组扩增或突变，是其在膀胱癌体内和体外表达增强的原因。此外，临床病理学分析表明，MMP11上调与膀胱癌患者的肿瘤进展和不良生存相关。讨论：这些研究结果表明，MMP11作为一种分泌蛋白，是膀胱癌诊断和预后的有前途的生物标志物。
Purpose: Bladder cancer is one of the leading causes of cancer death all over the world, and half of patients are diagnosed at advanced stages with poor therapeutic response. Thus, developing new biomarkers for bladder cancer diagnosis and prognosis is urgently needed.Materials and Methods: Bioinformatic and gene ontology (GO) analysis were employed to screen highly upregulated and secretory tumor markers in the TCGA BLCA cohort. IHC in tissue microarray and ELISA in cancer cell culture medium were used to validate the expression of putative biomarkers in bladder cancer. Bisulfite sequencing was used to detect DNA methylation status in the promoter of putative genes.Results: In this study, MMP11 is first identified as one of the most differentially expressed genes (DEGs) in bladder cancer by meta-analysis in a TCGA bladder cancer cohort. The strong upregulation of MMP11 is confirmed at protein levels in both bladder cancer patients and cell lines. Mechanistic studies reveal that MMP11 promoter hypomethylation, but not genomic amplification or mutation, accounts for its enhanced expression in bladder cancer both in vitro and in vivo. Moreover, clinicopathological analysis indicates that MMP11 upregulation is associated with the tumor progression and poor survival in bladder cancer patients.Discussion: These findings suggest that MMP11, as a secretory protein, is a promising biomarker for diagnosis and prognosis in bladder cancer.