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基质金属蛋白酶-1(MMP1)在人类肿瘤中的预后和免疫作用的泛癌分析。

A pan-cancer analysis of the prognostic and immunological roles of matrix metalloprotease-1 (MMP1) in human tumors.

作者信息

Mao Shuai, Xia Anliang, Tao Xuewen, Ye Dingde, Qu Jiamu, Sun Meiling, Wei Haowei, Li Guoqiang

机构信息

Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.

Department of Hepatobiliary Surgery, Medicine School of Southeast University Nanjing Drum Tower Hospital, Nanjing, China.

出版信息

Front Oncol. 2023 Jan 13;12:1089550. doi: 10.3389/fonc.2022.1089550. eCollection 2022.

Abstract

OBJECTIVE

Cancer remains the leading killer of human health worldwide. It has been shown that matrix metalloproteinase-1(MMP1) is related to poor prognosis in cancers such as BRCA, CESC and COAD. However, systematic pan-cancer analysis about the prognostic and immunological roles of MMP1 has not been explored. Here, the purpose of this study was to investigate the prognostic and immunological roles of MMP1 in pan-cancer and confirm cancer-promoting effect in pancreatic cancer.

METHODS

In our study, bioinformatics were first used to analyze data from multiple databases. Then, several bioinformatics tools were utilized to investigate the role of MMP1 in 33 tumor types. Finally, molecular biology experiments were carried out to prove the cancer-promoting effect of MMP1 in pancreatic cancer.

RESULTS

MMP1 expression was higher in tumor tissues than in control tissues in most tumor types. High expression of MMP1 was associated with poor overall survival (OS) and disease-free survival (DFS) in some tumor types. Further analysis of MMP1 gene mutation data showed that MMP1 mutations significantly influenced the prognosis of STAD. In addition, MMP1 expression was closely related to cancer-associated fibroblast (CAFs) infiltration in a variety of cancers and played an important role on immune infiltration score, tumor mutational burden (TMB) and microsatellite instability (MSI). Gene Ontology enrichment analysis indicated that these 20 genes were mainly related to extracellular structure organization/extracellular matrix organization/extracellular matrix disassembly/collagen metabolic process in the enriched biological processes. Finally, molecular biology experiments confirmed the cancer-promoting effect of MMP1 in pancreatic cancer.

CONCLUSIONS

Our pan-cancer analysis comprehensively proved that MMP1 expression is related with clinical prognosis and tumor immune infiltration, and MMP1 can become a prognostic and immunological biomarker.

摘要

目的

癌症仍然是全球人类健康的主要杀手。研究表明,基质金属蛋白酶-1(MMP1)与乳腺癌、子宫颈癌和结肠癌等癌症的预后不良有关。然而,尚未对MMP1的预后和免疫作用进行系统性的泛癌分析。本研究旨在探讨MMP1在泛癌中的预后和免疫作用,并证实其在胰腺癌中的促癌作用。

方法

在本研究中,首先利用生物信息学分析来自多个数据库的数据。然后,使用多种生物信息学工具研究MMP1在33种肿瘤类型中的作用。最后,进行分子生物学实验以证明MMP1在胰腺癌中的促癌作用。

结果

在大多数肿瘤类型中,肿瘤组织中MMP1的表达高于对照组织。在某些肿瘤类型中,MMP1的高表达与总生存期(OS)和无病生存期(DFS)不良相关。对MMP1基因突变数据的进一步分析表明,MMP1突变显著影响了胃癌的预后。此外,MMP1的表达与多种癌症中癌症相关成纤维细胞(CAFs)的浸润密切相关,并且在免疫浸润评分、肿瘤突变负担(TMB)和微卫星不稳定性(MSI)方面发挥重要作用。基因本体富集分析表明,在富集的生物学过程中,这20个基因主要与细胞外结构组织/细胞外基质组织/细胞外基质分解/胶原代谢过程有关。最后,分子生物学实验证实了MMP1在胰腺癌中的促癌作用。

结论

我们的泛癌分析全面证明,MMP-1表达与临床预后和肿瘤免疫浸润相关,并且MMP1可以成为一种预后和免疫生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b6/9885257/04481d2f535b/fonc-12-1089550-g001.jpg

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