Wang Zehao, Yu Tianlun, Liu Yuqiao, Wu Yufan, Hu Jingqing
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Clinical Laboratory, Kunshan Rehabilitation Hospital, Zhou Shi Branch, Kunshan Traditional Chinese Medicine Hospital, Kunshan, China.
Front Pharmacol. 2025 Jun 4;16:1586921. doi: 10.3389/fphar.2025.1586921. eCollection 2025.
Palmitoylation, a critical post-translational modification, regulates protein localization and function in cancer. However, its role in glioma progression, immune modulation, and prognosis remains poorly understood.
We integrated transcriptomic, clinical, and mutation data from multicenter cohorts to analyze 30 palmitoylation-related genes in low-grade gliomas (LGG). Consensus clustering, differential expression analysis, and LASSO regression were employed to define palmitoylation clusters, identify prognostic genes, and construct a risk signature. The evaluation of immune infiltration and immunotherapy efficacy was further conducted across different risk groups. In the palmitoylation-related risk model, IGFBP2 was functionally validated through siRNA-mediated knockdown and a series of assays, including EdU incorporation, cell cycle analysis, wound healing, and transwell migration assays.
Two palmitoylation clusters (A/B) were identified, with Cluster B exhibiting poorer survival ( < 0.001), enriched JAK-STAT signaling, and elevated immune infiltration (M1/M2 macrophages, CD8 T cells). A five-gene prognostic signature (, , , , ) demonstrated robust predictive accuracy in training (AUC 0.92-0.94) and validation cohorts (AUC 0.68-0.83). High-risk patients showed upregulated PD-1, PD-L1, and CTLA4 ( < 0.001) and higher TIDE scores, indicative of immune dysfunction. IGFBP2 knockdown suppressed glioma cell proliferation ( < 0.01) and migration ( < 0.001), linking it to tumor aggressiveness.
Palmitoylation plays a pivotal role in LGG progression by influencing immune evasion and stromal interactions. The developed prognostic signature and nomogram offer practical tools for risk stratification in clinical settings, with IGFBP2 identified as a promising therapeutic target. These insights highlight the potential of palmitoylation-focused therapies to enhance outcomes for LGG patients.
棕榈酰化是一种关键的翻译后修饰，可调节癌症中的蛋白质定位和功能。然而，其在胶质瘤进展、免疫调节和预后中的作用仍知之甚少。
我们整合了多中心队列的转录组、临床和突变数据，以分析低级别胶质瘤（LGG）中30个与棕榈酰化相关的基因。采用共识聚类、差异表达分析和LASSO回归来定义棕榈酰化簇、鉴定预后基因并构建风险特征。进一步对不同风险组进行免疫浸润和免疫治疗疗效评估。在与棕榈酰化相关的风险模型中，通过siRNA介导的敲低和一系列实验，包括EdU掺入、细胞周期分析、伤口愈合和transwell迁移实验，对IGFBP2进行了功能验证。
鉴定出两个棕榈酰化簇（A/B），簇B的生存率较差（<0.001），JAK-STAT信号富集，免疫浸润增加（M1/M2巨噬细胞、CD8 T细胞）。一个五基因预后特征（，，，，）在训练队列（AUC 0.92 - 0.94）和验证队列（AUC 0.68 - 0.83）中显示出强大的预测准确性。高危患者的PD-1、PD-L1和CTLA4上调（<0.001），TIDE评分更高，表明免疫功能障碍。IGFBP2敲低抑制了胶质瘤细胞的增殖（<0.01）和迁移（<0.001），将其与肿瘤侵袭性联系起来。
棕榈酰化通过影响免疫逃逸和基质相互作用在LGG进展中起关键作用。所开发的预后特征和列线图为临床环境中的风险分层提供了实用工具，IGFBP2被确定为有前景的治疗靶点。这些见解突出了以棕榈酰化为重点的疗法改善LGG患者预后的潜力。
