Yu Jing, He Zhen, He Xiaowen, Luo Zhanhao, Lian Lei, Wu Baixing, Lan Ping, Chen Haitao
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, China.
Front Oncol. 2021 Nov 5;11:771099. doi: 10.3389/fonc.2021.771099. eCollection 2021.
Previous 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.
In 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.
We 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.
This study implied that MMP11, MMP14, MMP17, and MMP19 are potential targets of precision therapy for patients with colorectal cancer.
先前的研究表明,基质金属蛋白酶(MMP)家族基因在肿瘤侵袭、新生血管生成和转移中起重要作用。然而,24种MMP在结直肠癌中的不同表达模式和预后价值尚待分析。
在本研究中,通过整合公共数据库和我们的数据,我们首先研究了结直肠癌患者中MMP的表达水平和蛋白水平。然后,利用TCGA和GEO数据集,我们评估了MMP与结直肠癌临床病理参数和预后的相关性。最后,通过使用cBioPortal在线工具,我们分析了MMP的改变,并对MMP及其附近基因进行了网络和通路分析。
我们发现,在公共数据集和我们的样本中,MMP1、MMP3、MMP7、MMP9 - MMP12和MMP14持续上调。而在公共数据集和我们的样本中,MMP28持续下调。在临床病理分析中,上调的MMP11、MMP14、MMP16、MMP17、MMP19和MMP23B与更高的肿瘤分期显著相关。在生存分析中,上调的MMP11、MMP14、MMP17和MMP19与更短的无进展生存期(PFS)和更短的无复发生存期(RFS)显著相关。
本研究表明,MMP11、MMP14、MMP17和MMP19是结直肠癌患者精准治疗的潜在靶点。