Association of TIMP-2 Expression with Postoperative Prognosis in Hepatocellular Carcinoma Patients and Development of a Predictive Model.

[PURPOSE] This study aimed to investigate the expression of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in postoperative patients with hepatocellular carcinoma (HCC), its relationship with prognosis, and to build a nomogram prediction model for overall survival (OS) and disease-free survival (DFS) based on TIMP-2 expression.

[PATIENTS AND METHODS] Expression profile data from HCC-related datasets were obtained from the Gene Expression Omnibus to analyze the correlation between TIMP-2 and HCC survival and prognosis, and its relationship with the HCC tumor immune microenvironment. Overall, 118 patients who underwent radical surgery for HCC were included retrospectively. To investigate the relationship between TIMP-2 expression and the clinicopathological characteristics and prognosis of patients with HCC, Cox regression analysis was used to determine the independent prognostic factors for DFS and OS. A nomogram prediction model for OS and DFS after HCC was established based on TIMP-2.

[RESULTS] In the TIMP-2 high expression group, CD4+ T cells, CD8+ T lymphocytes, macrophages, and natural killer cells were the predominant infiltrates. The 1-, 2-, 3-, and 5-year survival and DFS rates in the low TIMP-2 expression group were higher than in the high TIMP-2 expression group (<0.01). TIMP-2, neutrophil-to-lymphocyte (NLR), and tumor count were independent risk factors for OS (<0.05), while NLR, liver cirrhosis, and ECOG score were independent risk factors for DFS (<0.05). A TIMP-2-based nomogram for OS and DFS demonstrated good discrimination, calibration capabilities, and clinical utility as confirmed by ROC curves, calibration maps, and DCA in both training and verification sets.

[CONCLUSION] TIMP-2 may be involved in regulating the immune microenvironment as an immune inflammation-related gene in HCC. The nomogram prediction model of OS and DFS after HCC was established based on TIMP-2, providing a tool to predict the survival prognosis and recurrence risk of patients after HCC.