Gao Hanyuan, Qiu Yanru, Zheng Xueqin, Xu Tianwen, Liu Guangjian
Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Front Oncol. 2024 Sep 16;14:1466319. doi: 10.3389/fonc.2024.1466319. eCollection 2024.
Bladder cancer (BLCA) is a prevalent urinary tract malignancy with a high propensity for recurrence and chemoresistance. The molecular mechanisms underlying its progression and response to therapy have not been fully elucidated.
We conducted a multifaceted analysis, integrating immunohistochemical (IHC) staining, bioinformatics evaluation using TCGA and CCLE databases, and assays using the BLCA cell lines 5637 and T24. RAC3 expression was assessed relative to clinical and pathological features. Functional enrichment analyses and gene set enrichment analysis (GSEA) were performed to identify associated biological processes and pathways. The impacts of RAC3 on cell proliferation, migration, invasion, and the immune microenvironment were evaluated using siRNA knockdown, CCK-8, Transwell, wound healing and colony formation assays.
Elevated RAC3 expression was significantly correlated with an advanced tumor stage, lymph node metastasis, and poor prognosis for BLCA patients. The functional enrichment analysis implicated RAC3 in immune cell infiltration and immune checkpoint mechanisms. Notably, RAC3 knockdown significantly reduced the proliferative, migratory, and invasive capabilities of BLCA cells. These effects were reversed by the overexpression of RAC3. Additionally, RAC3 expression was linked to chemoresistance, with high RAC3 expression predicting resistance to certain therapeutic agents. The TIDE algorithm indicated that RAC3 expression could be a predictive biomarker for the immunotherapy response.
RAC3 was identified as a potential therapeutic target and biomarker of BLCA, as its expression significantly influenced tumor progression, the immune response, and chemosensitivity. Targeting RAC3 may provide a novel strategy for the management of BLCA, particularly for patients resistant to conventional therapies. Further research is essential to elucidate the detailed mechanisms of RAC3 in BLCA and explore its clinical application in precision medicine.
膀胱癌（BLCA）是一种常见的泌尿系统恶性肿瘤，具有较高的复发和化疗耐药倾向。其进展及对治疗反应的分子机制尚未完全阐明。
我们进行了多方面分析，整合免疫组织化学（IHC）染色、使用TCGA和CCLE数据库的生物信息学评估以及使用BLCA细胞系5637和T24的实验。评估RAC3表达与临床和病理特征的相关性。进行功能富集分析和基因集富集分析（GSEA）以确定相关的生物学过程和通路。使用小干扰RNA敲低、CCK-8、Transwell、伤口愈合和集落形成实验评估RAC3对细胞增殖、迁移、侵袭和免疫微环境的影响。
RAC3表达升高与BLCA患者的肿瘤晚期、淋巴结转移及预后不良显著相关。功能富集分析表明RAC3参与免疫细胞浸润和免疫检查点机制。值得注意的是，RAC3敲低显著降低了BLCA细胞的增殖、迁移和侵袭能力。RAC3过表达可逆转这些作用。此外，RAC3表达与化疗耐药相关，高RAC3表达预示对某些治疗药物耐药。TIDE算法表明RAC3表达可能是免疫治疗反应的预测生物标志物。
RAC3被确定为BLCA的潜在治疗靶点和生物标志物，因为其表达显著影响肿瘤进展、免疫反应和化疗敏感性。靶向RAC3可能为BLCA的治疗提供一种新策略，特别是对于对传统疗法耐药的患者。进一步研究对于阐明RAC3在BLCA中的详细机制并探索其在精准医学中的临床应用至关重要。
