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RAC1 作为预后因素并与肝细胞癌中的免疫浸润相关

英文原题:RAC1 serves as a prognostic factor and correlated with immune infiltration in liver hepatocellular carcinoma.

查看英文原题

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

PubMed 2024/09/12(内容时间) J Cancer Res Clin Oncol Q2 · IF 3.3(JCR 2025)

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研究概要

这些发现表明,RAC1 表达促进 LIHC 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 潜在的预后生物标志物,与癌症进展和肿瘤免疫细胞浸润均相关。

研究思路结论见上方概要

肝细胞癌(LIHC)因诊断晚和缺乏有效疗法而后果严重。目前,用于LIHC诊断和预后的潜在生物标志物尚未得到系统评估。既往研究报道,RAC1在多种肿瘤微环境中与B细胞受体信号通路相关,但其与LIHC的关系仍不清楚。我们研究了RAC1与LIHC预后及免疫浸润微环境之间的关系,探索其作为该类型癌症预后生物标志物的潜力。

在本研究中,我们利用Wilcoxon符号秩检验和逻辑回归分析癌症基因组图谱(TCGA)数据,以评估RAC1表达与LIHC患者临床特征之间的关联。此外,采用Kaplan-Meier和Cox回归方法确认RAC1表达水平对总生存期的影响。使用免疫组织化学验证LIHC中RAC1蛋白表达。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。

RAC1在LIHC组织中的表达水平显著高于正常组织。RAC1高表达与晚期病理分期密切相关,并被确定为独立影响总生存期的负面因素。在细胞和动物水平上,RAC1敲低均显著抑制了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,提示RAC1可能促进肿瘤免疫抑制微环境的恶化,并可能导致患者生存期缩短。

展开英文摘要原文

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.

论文信息

作者
Li Y、Gu A、Yang L、Wang Q
第一作者单位
Department of Chemotherapy, The Second Hospital of Nanjing,Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.China
通讯作者单位
Department of Chemotherapy, The Second Hospital of Nanjing,Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. luoriwangchao@126.com.China
期刊
Journal of cancer research and clinical oncology2024 Sep 12
原文标识
PubMed 39264423 · DOI 10.1007/s00432-024-05933-w