Role of Dysregulated Immune Biomarkers in Hepatocellular Carcinoma Metastasis: A Systematic Meta-Analysis Review

The liver plays a crucial role in immune system regulation, but dysregulation of immunological networks contributes to chronic liver diseases like hepatocellular carcinoma. This malignant tumor is the third leading cause of cancer death. An imbalanced immune system, characterized by alterations in immune cell count, cytokine levels, and inhibitory receptors, can impact metastasis by suppressing the immune system's ability to fight cancer cells. This study aims to investigate the potential biomarkers playing a crucial role in immune dysregulation resulting in hepatocellular carcinoma metastasis. A comprehensive and systematic literature review was conducted using both free words and search terms. The data extraction was then performed by a thorough literature screening. Next, the meta-analysis was performed using the metabin function of the meta library in R to evaluate the patient cases reporting metastasis in the event group. A total of 1,008 cases were considered, with 357 as events and 651 as nonevents. The results of the meta-analysis demonstrated the significant role of biomarkers in immune dysregulation causing metastasis (risk ratio = 0.54, 95% confidence interval: 0.4972, 0.6048, I ²  = 92.4%, p  < 0.01). In addition to the immune dysregulation explored in this study, the impact of tumor size on hepatocellular carcinoma progression and metastasis is a crucial consideration. A notable difference of 41 more cases was reported for larger tumor sizes. The study integrates immune dysregulation biomarkers and tumor size factors influencing hepatocellular carcinoma metastasis, offering valuable insights for future research and therapeutic interventions for improved clinical outcomes.