Matrix metalloproteinase 1 is a poor prognostic biomarker for patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database. The KEGG enrichment pathway using differentially expressed genes included extracellular matrix-receptor interaction, which was correlated with MMPs. We found that among the MMP family, only MMP1, MMP3, MMP8, MMP9, MMP11, MMP12, MMP14, MMP15, MMP20, MMP21, and MMP24 significantly increased in HCCs compared with adjacent tissues. Crucially, survival and univariate analyses indicated that only MMPs 1, 9, 12, and 14 predict poor overall survival; however, multivariate Cox analysis and a nomogram demonstrated that only MMP1 is a poor prognostic biomarker for HCCs. In addition, we observed significant enrichment of uncharacterized cells but decreased macrophages in HCC tissues. Consistent with decreased macrophages in HCCs, MMP1 was negatively associated with macrophages but positively correlated with uncharacterized cells, indicating that the main producer of MMP1 is uncharacterized cells. Furthermore, MMP1 expression was negatively correlated with immune responses of HCCs. Taken together, our findings indicated that MMP1 is a poor and predominant prognostic biomarker for patients with HCC and that anti-MMP1 may be a novel therapy that is worth studying in depth.

Automated summary

This study found that MMP1 is a poor prognostic and predominant biomarker for patients with HCC. Anti-MMP1 may be a novel therapy worth studying.