Abstract
Background Matrix metalloproteinase-9 (MMP-9) can degrade the extracellular matrix and participate in tumor progression. The relationship between MMP-9 and immune cells has been reported in various malignant tumors. However, there is a lack of comprehensive pan-cancer studies on the relationship between MMP-9 and cancer prognosis and immune infiltration. Method We used data from TCGA and GTEx databases to comprehensively analyze the differential expression of MMP-9 in normal and cancerous tissues. Survival analysis was performed to understand the prognostic role of MMP-9 in different tumors. We then analyzed the expression of MMP-9 across different tumors and at different clinical stages. Based on the results, we assessed the correlation between MMP-9 expression and immune-associated genes and immunocytes. Finally, we calculated the tumor mutation burden (TMB) of 33 cancer types and analyzed the correlation between MMP-9 and TMB, DNA microsatellite instability, and DNA repair genes. Results MMP-9 significantly affected the prognosis and metastasis of various cancers. It was associated based on overall survival, disease-specific survival in five tumors, progression-free interval in seven tumors, and clinical stage in eight tumors, as well as with prognosis and metastasis in adrenocortical carcinoma and kidney renal clear cell carcinoma. It was also coexpressed with immune-related genes and DNA repair genes. The expression of MMP-9 was positively correlated with the markers of T cells, tumor-associated macrophages, Th1 cells, and T cell exhaustion. Furthermore, MMP-9 expression was highly correlated with macrophage M0 in 28 tumors. In addition, its expression was associated with TMB in eight cancer types and DNA microsatellite instability in six cancer types. Conclusion MMP-9 is related to immune infiltration in pan-cancer and can be used as a biomarker related to cancer prognosis and metastasis. Our findings provide prognostic molecular markers and new ideas for immunotherapy.
Highlights
Matrix metalloproteinase-9 (MMP-9) [1] is a significant matrix metalloproteinase that is involved in many biological processes by degrading the extracellular matrix
Shorter PFI in Adrenocortical carcinoma bladder urothelial carcinoma (BLCA) (ACC) (P = 0:002), uveal melanoma (UVM) (P = 0:009), KIRC (P = 0:001), thyroid carcinoma (THCA) (P = 0:025), and glioblastoma multiforme (GBM) (P = 0:021) and longer PFI in DLBC (P = 0:004) and CESC (P = 0:031) (Figures 5(a)–5(g)). These results indicate that high MMP-9 expression might be a risk factor for poor prognosis in ACC, BLCA, KIRC, liver hepatocellular carcinoma (LIHC), UVM, THCA, and GBM, while low MMP-9 expression might be a risk factor for poor prognosis in DLBC, uterine corpus endometrial carcinoma (UCEC), skin cutaneous melanoma (SKCM), and CESC
Through survival analysis and clinical correlation analysis, we found that MMP-9 was related to poor prognosis and metastasis in ACC and KIRC
Summary
Matrix metalloproteinase-9 (MMP-9) can degrade the extracellular matrix and participate in tumor progression. We assessed the correlation between MMP-9 expression and immune-associated genes and immunocytes. MMP-9 significantly affected the prognosis and metastasis of various cancers It was associated based on overall survival, disease-specific survival in five tumors, progression-free interval in seven tumors, and clinical stage in eight tumors, as well as with prognosis and metastasis in adrenocortical carcinoma and kidney renal clear cell carcinoma. It was coexpressed with immune-related genes and DNA repair genes. The expression of MMP9 was positively correlated with the markers of T cells, tumor-associated macrophages, Th1 cells, and T cell exhaustion. Our findings provide prognostic molecular markers and new ideas for immunotherapy
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