Department of Chemotherapy, The Second Hospital of Nanjing，Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
Department of Hepatobiliary Surgery, The Second Hospital of Nanjing，Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
J Cancer Res Clin Oncol. 2024 Sep 12;150(9):418. doi: 10.1007/s00432-024-05933-w.
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.
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.
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.
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.
肝细胞癌（LIHC）由于诊断较晚和缺乏有效治疗方法，后果严重。目前，LIHC 诊断和预后的潜在生物标志物尚未得到系统评估。先前的研究表明，RAC1 与各种肿瘤微环境中的 B 细胞受体信号通路有关，但它与 LIHC 的关系尚不清楚。我们研究了 RAC1 与 LIHC 预后和免疫浸润微环境之间的关系，探索了其作为这种癌症的预后生物标志物的潜力。
在这项研究中，我们使用 Wilcoxon 符号秩检验和逻辑回归分析了来自癌症基因组图谱（TCGA）的数据，以评估 RAC1 表达与 LIHC 患者临床特征之间的关联。此外，还使用 Kaplan-Meier 和 Cox 回归方法证实 RAC1 表达水平对总生存的影响。使用免疫组织化学验证 RAC1 蛋白在 LIHC 中的表达。我们构建了 RAC1 敲低的 LIHC 细胞，并在细胞和动物水平上研究了 RAC1 蛋白对细胞增殖和迁移的影响。
与正常组织相比，LIHC 组织中 RAC1 的表达水平显著升高。高 RAC1 表达与较晚的病理分期密切相关，被确定为独立的负向影响总生存的因素。在细胞和动物水平上，RAC1 敲低均显著抑制 LIHC 细胞的增殖和迁移。此外，RAC1 表达与肿瘤微环境中 Th2 细胞和巨噬细胞的浸润呈正相关，表明 RAC1 可能导致肿瘤免疫抑制微环境恶化，并可能导致患者生存时间缩短。
这些发现表明，RAC1 表达促进 LIHC 的增殖和迁移，并影响肿瘤微环境中免疫细胞浸润的格局。基于这些结果，RAC1 被提出作为 LIHC 的潜在预后生物标志物，与癌症进展和肿瘤免疫细胞浸润有关。
