〔Abstract〕 To characterize MMP12 as a pan-cancer marker and assess its screening value as a tumor serum marker. Methods Bioinformatics tools such as GEPIA2 , GSCA , cBioPortal , and GeneMANIA were used to analyze the pan-cancer features of MMP12 in TCGA datasets , including encompassing differential gene expression analysis , prognostic analysis , DNA methylation analysis , gene structural variation analysis and immune microenvi- ronment analysis . Furthermore , serum samples we collected from patients with lung adenocarcinoma , breast inva- sive carcinoma , esophageal squamous cell carcinoma , stomach adenocarcinoma , liver hepatocellular carcinoma , and healthy individuals . ELISA was used to detect MMP12 expression in serum , and the screening performance was evaluated using the area under the ROC curve . Additionally , we followed up 28 ESCC patients and compared serum MMP12 levels between 19 patients with disease progression and 9 patients with stable disease . Results The pan- cancer feature analysis revealed a significant negative correlation between MMP12 mRNA expression and its promot-er DNA methylation (P < 0. 05) , as well as a positive correlation with gene copy number variations (P < 0. 05) . MMP12 mRNA expression was up-regulated in 14 cancer tissues compared to normal tissues next to cancer (P < 0. 05) and was associated with poor prognosis of cancer patients (P < 0. 05) . Immunocorrelation analysis showed that MMP12 was significantly associated with immunity , infiltration of stromal cells , tumor mutational burden (TMB) and microsatellite instability (MSI) (P < 0. 05) . ROC curve analysis indicated that MMP12 could serve as a potential biomarker for screening lung adenocarcinoma , breast invasive carcinoma , esophageal squamous cell car- cinoma , stomach adenocarcinoma , and liver hepatocellular carcinoma. In a 30-month follow-up study of esophageal squamous cell carcinoma patients , the expression of MMP12 was higher in the disease progression group than that in the stable group . Conclusion MMP12 serves as a potential prognostic and screening marker of pan-cancer.