Pan-cancer analysis reveals the associations between MMP13 high expression and carcinogenesis and its value as a serum diagnostic marker.

ABSTRACT

BACKGROUND: Matrix metalloproteinase-13 (MMP13) is a member of the endopeptidase matrix metalloproteinase family, which is involved in many normal physiological processes and even tumorigenesis. However, its co-carcinogenic signature in different cancers is not fully understood. METHODS: In this study, we first analyzed the expression of MMP13 in pan-cancer and its association with prognosis, immune infiltration, and cancer-related signaling pathways through integrated bioinformatics. Furthermore, western blotting (WB) was used to verify the expression of MMP13 and epithelial-mesenchymal transition (EMT) factors in cancer tissues. Finally, the value of MMP13 as a serum diagnostic marker was analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: MMP13 expression is frequently upregulated in multiple cancers that always indicate an adverse prognosis. MMP13 undergoes comprehensive genetic alterations and promoter methylation reduction in various tumors. Additionally, immune correlation analysis showed that MMP13 expression was significantly associated with TMB, MSI, and tumor immune infiltration. Pathway enrichment analysis showed that MMP13 upregulation was correlated with activation of the EMT signaling pathway, which was verified by WB in lung adenocarcinoma tissues. Most importantly, ELISA results showed that serum MMP13 levels could be used for the diagnosis of multiple tumors, including BRCA, HNSC, LUAD, and LUSC, with the area under the curve (AUC) values of 0.8494, 0.9259, 0.7144, and 0.8575, respectively. CONCLUSIONS: MMP13 is often overexpressed across cancers and predicts poor prognosis, with the potential as a therapeutic target. Furthermore, the up-regulation of its expression can be effectively reflected in the serum protein level, thus serving as a valuable diagnostic marker.