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. 2021 Sep 17:11:717606.
doi: 10.3389/fonc.2021.717606. eCollection 2021.

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors

Minde Li  1 , Shaoyang Li  1 , Lin Zhou  1 , Le Yang  1 , Xiao Wu  1 , Bin Tang  1 , Shenhao Xie  1 , Linchun Fang  1 , Suyue Zheng  1 , Tao Hong  1
Affiliations
Free PMC article

Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors

Minde Li et al. Front Oncol. .
Free PMC article

Abstract

Background: Matrix metalloproteinase 14 (MMP14) is a member of the MMP family, which interacts with tissue inhibitors of metalloproteinase (TIMPs), and is involved in normal physiological functions such as cell migration, invasion, metastasis, angiogenesis, and proliferation, as well as tumor genesis and progression. However, there has been a lack of relevant reports on the effect of MMP14 across cancers. This study aims to explore the correlation between MMP14 and pan-cancer prognosis, immune infiltration, and the effects of pan-cancer gene mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, and immune checkpoint genes.

Methods: In this study, we used bioinformatics to analyze data from multiple databases, including The Cancer Genome Atlas (TCGA), ONCOMINE, and Kaplan-Meier plotter. We investigated the relationship between the expression of MMP14 in tumors and tumor prognosis, the relationship between MMP14 expression and tumor cell immune infiltration, and the relationship between MMR gene MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.

Results: MMP14 expression is highly associated with the prognosis of a variety of cancers and tumor immune invasion and has important effects on pan oncologic MMR, MSI, TMB, DNA methylation, and immune checkpoint genes.

Conclusion: MMP14 is highly correlated with tumor prognosis and immune invasion and affects the occurrence and progression of many tumors. All of these results fully indicate that MMP14 may be a biomarker for the prognosis, diagnosis, and treatment of many tumors and provide new ideas and direction for subsequent tumor immune research and treatment strategies.

Keywords: MMP14; immune infiltration; pan-cancer analysis; prognosis; tumor immune microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Differences in MMP14 expression in tumor tissues and normal tissues across cancers. (A) The Oncomine database was used to analyze the expression of MMP14 in tumor tissues and normal tissues. The number in each cell is the total amount in the dataset. (B) Analysis and comparison of MMP14 expression in different tumor tissues and normal tissues in TCGA database. *P < 0.05, **P < 0.01 ***P < 0.001.
Figure 2
Figure 2
The relationship between the expression of matrix metalloproteinase 14 (MMP14) and the overall survival (OS) and prognosis of pan-cancer was analyzed. (A) The correlation between MMP14 expression and OS in different cancer types of The Cancer Genome Atlas (TCGA) was analyzed. The red part represents the risk ratio. Due to the limited sample size, the parameters and hazard ratio could not be calculated with short bars, and the red font indicates p < 0.05. (B) Kaplan–Meier analysis was used to generate a survival curve for the prognostic effect of MMP14 expression on pan-cancer. OS, overall survival.
Figure 3
Figure 3
The expression of matrix metalloproteinase 14 (MMP14) was correlated with disease-free survival (DFS), and prognosis was analyzed by disease-free interval (DFI). The expression of MMP14 and the overall survival rate of pan-cancer were analyzed by DFI. (A) Correlation analysis of MMP14 expression and DFI in different cancer types of The Cancer Genome Atlas (TCGA). The red part represents the risk ratio. Due to the limited sample size, the parameters and hazard ratio could not be calculated with short bars, and the red font indicates p < 0.05. (B) Kaplan–Meier analysis was used to generate a survival curve for the prognostic effect of MMP14 expression on pan-cancer. DFI, disease-free interval survival.
Figure 4
Figure 4
The expression of matrix metalloproteinase 14 (MMP14) and the prognosis of disease-specific survival (DSS) were analyzed. The relationship between MMP14 expression and disease-free survival was analyzed by DSS. The expression of MMP14 and the overall survival rate of pan-cancer were analyzed by DSS. (A) Correlation analysis of MMP14 expression and DSS in different cancer types of The Cancer Genome Atlas (TCGA). The red part represents the risk ratio. Due to the limited sample size, the parameters and hazard ratio could not be calculated with short bars, and the red font indicates p < 0.05. (B) Kaplan–Meier analysis was used to generate a survival curve for the prognostic effect of MMP14 expression on pan-cancer. DSS, disease-specific survival.
Figure 5
Figure 5
The relationship between MMP14 expression and PFI prognosis was analyzed. The expression of MMP14 and prognosis of pan cancer disease-specific survival were analyzed by PFI. The relationship between MMP14 expression and disease-free survival was analyzed by DSS. The expression of MMP14 and the overall survival rate of pan cancer patients were analyzed by PFI. (A) Correlation analysis of MMP14 expression and PFI in different cancer types of TCGA; the red part represents the risk ratio. Due to the limited sample size, the parameters and hazard ratio could not be calculated with short bars, and the red font indicates P < 0.05. (B) Kaplan–Meier analysis was used to generate a survival curve for the prognostic effect of MMP14 expression on pan cancer. PFI, progression-free interval survival.
Figure 6
Figure 6
The expression of matrix metalloproteinase 14 (MMP14) in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), and colon adenocarcinoma (COAD) was correlated with the level of immune infiltration (B cells, CD4 T cells, CD8 T cells, macrophages, dendritic cells, and neutrophils). Only in BLCA was the expression of MMP14 negatively correlated with B-cell infiltration, and the others were positively correlated with the six kinds of immune cell infiltration.
Figure 7
Figure 7
Relationship between the expression of matrix metalloproteinase 14 (MMP14) and immune score in pan-cancer. Only in adrenocortical carcinoma (ACC), skin cutaneous melanoma (SKCM), testicular germ cell tumor (TGCT), and thymoma (THYM) was the expression of MMP14 negatively correlated with immune cell infiltration, and the others were positively correlated with immune cell infiltration (in the case of p < 0.05).
Figure 8
Figure 8
Relationship between the expression of matrix metalloproteinase 14 (MMP14) and stromal score in pan-cancer. Only in skin cutaneous melanoma (SKCM) was the expression of MMP14 negatively correlated with immune cell infiltration, and the others were positively correlated with immune cell infiltration (p < 0.05).
Figure 9
Figure 9
The three tumors with the highest correlation between matrix metalloproteinase 14 (MMP14) expression and immune score and stromal score in the pan-cancer analysis. The expression of MMP14 is positively correlated with the infiltration levels of these immune cells.
Figure 10
Figure 10
Correlation analysis of MMP14 expression and 47 immune checkpoint genes in endemic cancer.MMP14 was associated with 38 immune checkpoint genes in PRAD, 36 in LGG, 33 in THCA and 24 in KICH. We also found that the immune checkpoint gene CD276 was significantly associated with MMP14 expression in 28 of 33 tumors (*P < 0.05, **P < 0.01 ***P < 0.001).
Figure 11
Figure 11
The expression of matrix metalloproteinase 14 (MMP14) was correlated with the expression of five mismatch repair (MMR) genes and four DNA methyltransferases. (A) Spearman correlation analysis was used to analyze the correlation between MMR gene expression and MMP14 expression in tumors (*p < 0.05, **p < 0.01, **p < 0.001). (B) Spearman correlation analysis was used to analyze the correlation between four DNA methyltransferases and MMP14 expression.
Figure 12
Figure 12
The expression of matrix metalloproteinase 14 (MMP14) was correlated with tumor mutational burden (TMB) and microsatellite instability (MSI). (A) Radar images were used to show the correlation between MMP14 expression and TMB. The black value represents the range, and the blue curve represents the correlation coefficient. (B) Radar images were used to show the correlation between MMP14 expression and MSI. The black value represents the range, and the red curve represents the correlation coefficient.
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