Research Paper Volume 15, Issue 6 pp 2115—2135
Pan-cancer analysis reveals the associations between MMP13 high expression and carcinogenesis and its value as a serum diagnostic marker
- 1 School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
- 2 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
- 3 Medical Pathology Center, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China
- 4 Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China
- 5 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- 6 Biological Molecular Information System Laboratory, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
Received: October 29, 2022 Accepted: March 8, 2023 Published: March 22, 2023
https://doi.org/10.18632/aging.204599How to Cite
Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
AUC: areas under the curves; BRCA: Breast invasive carcinoma; CA15-3: carbohydrate antigen 153; CCL20: chemokine CC ligand 20; CEA: carcinoembryonic antigen; CYFRA21-1: cytokeratin 19 fragment; DFI: disease-free interval; DSS: disease-specific survival; Elisa: enzyme-linked immune sorbent assay; EMT: epithelial-mesenchymal transition; HCC: hepatocellular carcinoma; HNSC: head and neck squamous cell carcinoma; IQR: Interquartile range; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MSI: Medical Services Insurance; OS: overall survival; PFS: progression-free survival; ROC: receiver operating characteristic curve; SCC: squamous cell carcinoma antigen; TCGA: Cancer Genome Atlas; TMB: tumor mutational burden.