Liao Si-Na, Li Ting, Liu Zhi-Hui, Luo Dong-Cheng, Long Xia-Wei, Liao Xiao-Li, Liu Jian-Lun
Day Oncology Unit, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Digestive Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
J Inflamm Res. 2025 Aug 26;18:11703-11736. doi: 10.2147/JIR.S530061. eCollection 2025.
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.
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.
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.
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.
本研究旨在调查基质金属蛋白酶-2组织抑制剂（TIMP-2）在肝细胞癌（HCC）术后患者中的表达情况，其与预后的关系，并基于TIMP-2表达构建总生存期（OS）和无病生存期（DFS）的列线图预测模型。
从基因表达综合数据库获取HCC相关数据集的表达谱数据，以分析TIMP-2与HCC生存及预后的相关性，及其与HCC肿瘤免疫微环境的关系。总体而言，回顾性纳入118例行HCC根治性手术的患者。为研究TIMP-2表达与HCC患者临床病理特征及预后的关系，采用Cox回归分析确定DFS和OS的独立预后因素。基于TIMP-2建立HCC术后OS和DFS的列线图预测模型。
在TIMP-2高表达组中，CD4+ T细胞、CD8+ T淋巴细胞、巨噬细胞和自然杀伤细胞是主要浸润细胞。TIMP-2低表达组的1年、2年、3年和5年生存率及DFS率均高于TIMP-2高表达组（<0.01）。TIMP-2、中性粒细胞与淋巴细胞比值（NLR）和肿瘤数量是OS的独立危险因素（<0.05），而NLR、肝硬化和美国东部肿瘤协作组（ECOG）评分是DFS的独立危险因素（<0.05）。基于TIMP-2的OS和DFS列线图在训练集和验证集中经ROC曲线、校准图和决策曲线分析证实具有良好的区分度、校准能力和临床实用性。
TIMP-2可能作为HCC中与免疫炎症相关的基因参与调节免疫微环境。基于TIMP-2建立了HCC术后OS和DFS的列线图预测模型，为预测HCC患者的生存预后和复发风险提供了一种工具。
