Xu Guangming, Jiang Yifan, Tu Zhenhua, Li Yu, Xu Xiaofeng, Tong Rongliang, Jiang Nan, Xie Kai, Chen Diyu, Wu Jian
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Department of Anesthesiology, Shaoxing People's Hospital, Zhejiang University, Shaoxing, 312000, China.
Clin Transl Oncol. 2025 Jun;27(6):2527-2543. doi: 10.1007/s12094-024-03756-2. Epub 2024 Dec 2.
Neutrophils, crucial in the immune system, have recently been implicated in promoting malignancy. RNA methylation, an essential epigenetic feature, plays a key role in tumor microenvironment (TME) reprogramming. However, the relationship between neutrophils and RNA methylation in hepatocellular carcinoma (HCC) remains unclear.
We analyzed single-cell sequencing data from HCC, focusing on cell subtype and TME construction. RNA methylation "writers" were selected, and their expression in neutrophils was evaluated. Two neutrophil subtypes (high/low RNA methylation) were identified. Differentially expressed genes (DEGs) between these subtypes were confirmed, leading to the identification of 6 molecular subtypes via consensus clustering. A prognostic scoring system was developed using LASSO Cox regression, resulting in a novel neutrophil RNA methylation (NRM) scoring system to assess TME heterogeneity and clinical features.
TRPM3, specifically expressed in HCC-infiltrating neutrophils, may regulate RNA modification in tumor pathogenesis. HCC patients were stratified into low/high-NRM score groups, further refined into an advanced NRM (a-NRM) score by incorporating lncRNA data. High a-NRM scores correlated with advanced TNM stage, higher pathological grade, and increased suppressive immune cells. A nomogram incorporating the a-NRM score demonstrated a concordance index indicative of good predictive performance.
The a-NRM score is a reliable predictor of prognosis and could guide treatment selection in HCC patients, enhancing clinical response to immunotherapy. TRPM3 also presents as a potential therapeutic target in HCC.
中性粒细胞在免疫系统中至关重要，最近被认为与促进恶性肿瘤有关。RNA甲基化是一种重要的表观遗传特征，在肿瘤微环境（TME）重编程中起关键作用。然而，肝细胞癌（HCC）中中性粒细胞与RNA甲基化之间的关系仍不清楚。
我们分析了来自HCC的单细胞测序数据，重点关注细胞亚型和TME构建。选择RNA甲基化“书写器”，并评估它们在中性粒细胞中的表达。鉴定出两种中性粒细胞亚型（高/低RNA甲基化）。确认了这些亚型之间的差异表达基因（DEG），通过一致性聚类鉴定出6种分子亚型。使用LASSO Cox回归开发了一种预后评分系统，从而产生了一种新的中性粒细胞RNA甲基化（NRM）评分系统，以评估TME异质性和临床特征。
TRPM3在HCC浸润的中性粒细胞中特异性表达，可能在肿瘤发病机制中调节RNA修饰。HCC患者被分为低/高NRM评分组，通过纳入lncRNA数据进一步细化为高级NRM（a-NRM）评分。高a-NRM评分与晚期TNM分期、更高的病理分级和增加的抑制性免疫细胞相关。纳入a-NRM评分的列线图显示出良好预测性能的一致性指数。
a-NRM评分是预后的可靠预测指标，可指导HCC患者的治疗选择，增强对免疫治疗的临床反应。TRPM3在HCC中也表现为潜在的治疗靶点。
