Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 236-244 http://medscipublisher.com/index.php/cge 236 Case Study Open Access Correlation Analysis of Postoperative Recurrence in Hepatocellular Carcinoma Patients and the Dynamic Evolution of the Tumor Immune Microenvironment Qiyan Lou, Xiaoying Xu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: xiaoying,xu@cuixi.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.5 doi: 10.5376/cge.2025.13.0024 Received: 02 Aug., 2025 Accepted: 07 Sep., 2025 Published: 15 Oct., 2025 Copyright © 2025 Lou and Xu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Lou Q.Y., and Xu X.Y., 2025, Correlation analysis of postoperative recurrence in hepatocellular carcinoma patients and the dynamic evolution of the tumor immune microenvironment, Cancer Genetics and Epigenetics, 13(5): 236-244 (doi: 10.5376/cge.2025.13.0024) Abstract This study explored the association between postoperative recurrence of hepatocellular carcinoma (HCC) and changes in the tumor immune microenvironment (TIME). The recurrence rate of liver cancer patients within five years after surgery can reach 50% to 70%, which has a significant impact on survival time. Recurrence is generally classified into two types: early (≤2 years) and late (>2 years). Early recurrence is often related to incomplete resection or tumor spread. At this time, the malignancy of the tumor is high and the treatment effect is poor. Late recurrence is often related to chronic diseases of the liver itself or the formation of new tumors. Tumor size, vascular invasion and alpha-fetoprotein level are important risk factors for recurrence. In patients with early recurrence, the tumor immune microenvironment (TIME) is often dominated by cells with immunosuppressive functions. In patients with advanced recurrence, CD8+T cells and dendritic cells are more likely to accumulate around the tumor. The dynamic changes of the tumor immune microenvironment (TIME) are a key factor in determining whether hepatocellular carcinoma (HCC) recurs, and also provide an important basis for risk prediction and personalized immunotherapy. Keywords Hepatocellular carcinoma; Postoperative recurrence; Tumor immune microenvironment; Immune escape; Risk prediction I Introduction Hepatocellular carcinoma (HCC) is a common primary malignant tumor of the liver and one of the important causes of cancer-related deaths worldwide (Jang et al., 2025). Although surgical and local treatment methods have been continuously advanced, liver cancer is prone to recurrence after surgery. The recurrence rate within five years is still as high as 50% - 70% after radical resection. The high recurrence rate seriously affects the long-term survival of patients and is currently the main clinical problem. Its occurrence is influenced by the characteristics of the tumor itself and the surrounding microenvironment (Chen et al., 2023; She et al., 2024). The tumor immune microenvironment (TIME) of liver cancer is a complex system composed of immune cells, interstitial components, cytokines and metabolic substances, etc., which interact with tumor cells. Affect the development and recurrence of the disease (Liu et al., 2023; Xie et al., 2025). The immunosuppressive components in TIME, such as regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages, etc., can help tumors evade immune attack, thereby promoting recurrence (Chen et al., 2020). Recent studies have found that the composition and distribution status of specific immune cells in tumors can serve as an important basis for predicting recurrence risk and response to immunotherapy (Yang et al., 2024; Jang et al., 2025). The dynamic changes of TIME during surgery or treatment, especially the alterations in immune cell infiltration and function, have gradually been regarded as important factors affecting postoperative recurrence (Wu et al., 2022; Yin et al., 2024; Wu et al., 2025). This study will analyze the relationship between postoperative recurrence in liver cancer patients and changes in the immune microenvironment. By integrating clinical, pathological and multi-omics data, it aims to identify immune markers related to recurrence and explain their modes of action, providing a basis for recurrence risk classification, adjuvant therapy and improvement of immunotherapy, thereby enhancing the therapeutic effect of patients. A deeper understanding of the connection between tumor recurrence and changes in the immune
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