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

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Abstract

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.

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All data generated in the study are included in the present article and supplementary data.

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Acknowledgements

We thank all of the authors listed in this manuscript.

Funding

This study was supported by Key Research Projects of Henan Higher Education Institutions (21A320049) and Henan Province Medical Science and Technology Research Project (SBGJ202102063).

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  1. Linping Xu and Hui Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Research and Foreign Affairs, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, China

    Linping Xu & Meimei Yan

  2. Department of Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, 450003, Henan, China

    Hui Yang

  3. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Wei Li

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Wei Li and Linping Xu designed, wrote, and edited the manuscript; analyzed the data; and finished the figures. Hui Yang revised the manuscript. Meimei Yan analyzed the data. All authors approved the final manuscript.

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10238_2022_897_MOESM1_ESM.tif

Supplementary Figure 1 (A) Upregulated KEGG pathways in HCC tissues. (B) Downregulated KEGG pathways in HCC tissues. (C) Upregulated GO terms in HCC tissues. (D) Downregulated GO terms in HCC tissues (TIF 7872 KB)

10238_2022_897_MOESM2_ESM.tif

Supplementary Figure 2 (A) The dotted line represents the median risk score and divides the patients into low-risk and high-risk groups. The curve of risk score. Survival status of the patients. More dead patients correspond to a higher risk score. Heat map of the expression profiles of the MMP3, -11, -15, -24, and -21 in the low- and high-risk groups. (B) Kaplan–Meier survival analysis of MMP3, -11, -15, -24, and -21 in the low- and high-risk groups. (C) Time-dependent ROC analysis of MMP3, -11, -15, -24, and -21 in the low- and high-risk groups (TIF 16729 KB)

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Xu, L., Yang, H., Yan, M. et al. Matrix metalloproteinase 1 is a poor prognostic biomarker for patients with hepatocellular carcinoma. Clin Exp Med 23, 2065–2083 (2023). https://doi.org/10.1007/s10238-022-00897-y

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