Pan-cancer Characterization Of MMP13 And Its Value As A Serum Diagnostic Marker

Background and purpose: Cancer is an important risk factor threatening human life and health,and early detection and treatment is the key to improve life expectancy.Matrix metalloproteinase-13(MMP13),a member of the matrix metalloproteinase family of endopeptidases,is a key molecule in regulating normal physiological processes and tumor development in the human body.However,its oncogenic characteristics in different cancers are not fully understood.Therefore,in this study,we initially explored the expression of MMP13 in 33 tumor types through multiple databases based on bioinformatics techniques and evaluated the correlation between its expression and prognosis,tumor mutational load(TMB),microsatellite instability(MSI),DNA methylation,tumor microenvironment,and immune-related genes in multiple cancer types.We further assessed the diagnostic value of MMP13 in the serum of specific tumors,such as non-small cell lung cancer.Methods: In this study,the datasets in The Cancer Genome Atlas(TCGA)database were analyzed using R language and various online websites including GEPIA2,GSCA,MEXPRESS,c Bio Portal,Gene MANIA,etc.First,the expression of MMP13 in pancancer was analyzed by R language and GEPIA2 online tool;then,the relationship between MMP13 expression and patient survival was analyzed by R language and GSCA online website;its expression was analyzed by R language as well as GSCA,MEXPRESS,c Bio Portal online websites in relation to gene variants,tumor mutation load(TMB),microsatellite instability(MSI),DNA methylation,and immune factors;we analyzed its correlation with cancer-related signaling pathways through GSCA,Gene MANIA,and visualized genes that are functionally related to MMP13;in addition,we used Western blotting(WB)techniques to validate the relationship between MMP13 and epithelialmesenchymal transition(EMT)-related markers in(EMT)-related markers 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 upregulated in a variety of cancers and always predicts a poor prognosis.MMP13 undergoes comprehensive genetic alterations and reduced promoter methylation in a variety of tumors.Furthermore,immune correlation analysis revealed that MMP13 expression was significantly associated with TMB,MSI and tumor immune infiltration.Pathway enrichment analysis showed that upregulation of MMP13 correlated with activation of the EMT signaling pathway,which was validated 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 area under the curve(AUC)values of 0.8494,0.9259,0.7144 and 0.8575,respectively.Conclusion: MMP13 occurs with varying degrees of upregulated expression in a variety of cancers and is predictive of poor prognosis,potentially serving as a target for tumor therapy.In addition,its upregulation of expression can be effectively reflected in serum protein levels,thus serving as a valuable diagnostic marker.