Table_4_Comprehensive Analysis of the Expression and Prognosis for MMPs in Human Colorectal Cancer.xlsx

BackgroundPrevious study implicated that genes of matrix metalloproteinase (MMP) family play an important role in tumor invasion, neoangiogenesis, and metastasis. However, the diverse expression patterns and prognostic values of 24 MMPs in colorectal cancer are yet to be analyzed.
MethodsIn this study, by integrating public database and our data, we first investigated the expression levels and protein levels of MMPs in patients with colorectal cancer. Then, by using TCGA and GEO datasets, we evaluated the association of MMPs with clinicopathological parameters and prognosis of colorectal cancer. Finally, by using the cBioPortal online tool, we analyzed the alterations of MMPs and did the network and pathway analyses for MMPs and their nearby genes.
ResultsWe found that, MMP1, MMP3, MMP7, MMP9–MMP12, and MMP14 were consistently upregulated in public dataset and our samples. Whereas, MMP28 was consistently downregulated in public dataset and our samples. In the clinicopathological analyses, upregulated MMP11, MMP14, MMP16, MMP17, MMP19, and MMP23B were significantly associated with a higher tumor stage. In the survival analyses, upregulated MMP11, MMP14, MMP17, and MMP19 were significantly associated with a shorter progression-free survival (PFS) time and a shorter relapse-free (RFS) time.
DiscussionThis study implied that MMP11, MMP14, MMP17, and MMP19 are potential targets of precision therapy for patients with colorectal cancer.

研究背景 既往研究表明，基质金属蛋白酶（matrix metalloproteinase，MMP）家族基因在肿瘤侵袭、新生血管生成及肿瘤转移中发挥关键作用。然而，结直肠癌中24种MMP基因的多样化表达模式与预后价值仍有待系统分析。
研究方法 本研究整合公共数据库与本团队的实验数据，首先探究了结直肠癌患者体内MMP基因的表达水平与蛋白表达水平。随后，借助癌症基因组图谱（The Cancer Genome Atlas，TCGA）与基因表达综合数据库（Gene Expression Omnibus，GEO）数据集，评估了MMP基因与结直肠癌患者临床病理参数及预后的相关性。最后，通过cBioPortal在线工具，分析了MMP基因的变异情况，并对MMP基因及其邻近基因开展了蛋白互作网络与通路富集分析。
研究结果 本研究发现，MMP1、MMP3、MMP7、MMP9-MMP12及MMP14在公共数据集与本团队样本中均呈显著上调表达；而MMP28在两类样本中均呈显著下调表达。临床病理分析显示，上调表达的MMP11、MMP14、MMP16、MMP17、MMP19及MMP23B与更高的肿瘤分期显著相关。生存分析结果表明，上调表达的MMP11、MMP14、MMP17及MMP19与更短的无进展生存期（progression-free survival，PFS）和无复发生存期（relapse-free survival，RFS）显著相关。
研究讨论 本研究提示，MMP11、MMP14、MMP17及MMP19可作为结直肠癌患者精准治疗的潜在靶点。