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Research Paper|Volume 16, Issue 10|pp 8667—8686

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma

Xingxing Yuan1,2, Liuxin Yang2, Jiawei Gao2, Xu Mao2, Yali Zhang3, Wei Yuan4
  • 1Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
  • 2Heilongjiang University of Chinese Medicine, Harbin, China
  • 3Zhang Yali Famous Traditional Chinese Medicine Expert Studio, Harbin, China
  • 4Department of Hepatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China
Received: September 28, 2023Accepted: April 3, 2024Published: May 16, 2024
https://doi.org/10.18632/aging.205832

Copyright: © 2024 Yuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells’ local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC.

Methods: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature.

Results: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster.

Conclusions: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.