RAC1 serves as a prognostic factor and correlated with immune infiltration in liver hepatocellular carcinoma

• Published in: Journal of cancer research and clinical oncology Vol. 150; no. 9; p. 418
• Main Authors: Li, Yuan, Gu, Aidong, Yang, Lili, Wang, Qingbo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 12.09.2024; Springer Nature B.V
• Subjects: Animals; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell survival; Diagnosis; Female; Helper cells; Hematology; Hepatocellular carcinoma; Humans; Immunohistochemistry; Infiltration; Internal Medicine; Leukocyte migration; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - immunology; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Macrophages; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Mice; Mice, Nude; Middle Aged; Oncology; Prognosis; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Rac1 protein; Signal transduction; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; RAC1; Overall survival; Liver hepatocellular carcinoma; Immune infiltration
• ISSN: 1432-1335; 0171-5216; 1432-1335
• DOI: 10.1007/s00432-024-05933-w

Background Hepatocellular carcinoma (LIHC) has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for the diagnosis and prognosis of LIHC have not been systematically evaluated. Previous studies have reported that RAC1 is associated with the B cell receptor signaling pathway in various tumor microenvironments, but its relationship with LIHC remains unclear. We investigated the relationship between RAC1 and the prognosis and immune infiltration microenvironment of LIHC, exploring its potential as a prognostic biomarker for this type of cancer. Methods In this study, we analyzed data from The Cancer Genome Atlas (TCGA) using the Wilcoxon signed-rank test and logistic regression to assess the association between RAC1 expression and clinical characteristics in LIHC patients. Additionally, Kaplan-Meier and Cox regression methods were employed to confirm the impact of RAC1 expression levels on overall survival. Immunohistochemistry was used to validate RAC1 protein expression in LIHC. We constructed RAC1 knockdown LIHC cells and studied the effects of RAC1 protein on cell proliferation and migration at both cellular and animal levels. Results RAC1 expression levels were significantly elevated in LIHC tissues compared to normal tissues. High RAC1 expression was strongly associated with advanced pathological stages and was identified as an independent factor negatively affecting overall survival. At both cellular and animal levels, RAC1 knockdown significantly inhibited the proliferation and migration of LIHC cells. Furthermore, RAC1 expression was positively correlated with the infiltration of Th2 cells and macrophages in the tumor microenvironment, suggesting that RAC1 may contribute to the deterioration of the tumor immunosuppressive microenvironment and potentially lead to reduced patient survival. Conclusion These findings indicate that RAC1 expression promotes LIHC proliferation and migration and influences the landscape of immune cell infiltration in the tumor microenvironment. Based on these results, RAC1 is proposed as a potential prognostic biomarker for LIHC, associated with both cancer progression and tumor immune cell infiltration.