NEDD1在肝细胞癌中的多组学分析：生物学功能、预后价值和临床意义
Multi-omics analysis of NEDD1 in hepatocellular carcinoma: biological function, prognostic value, and clinical significance.
摘要(中文译文)
神经前体细胞表达发育下调蛋白1（NEDD1）被认为与肿瘤发生相关，但其在肝细胞癌（HCC）中的作用尚不清楚。本研究旨在探讨NEDD1在HCC中的致癌作用、调控机制及肿瘤微环境相互作用。利用公共数据集（TCGA、GEO）和本机构临床样本进行多组学分析，包括表达与生存分析、表观遗传（DNA甲基化）和翻译后修饰（磷酸化）图谱分析、功能通路富集及药物敏感性预测。通过HCC细胞中NEDD1敲低及皮下异种移植模型进行功能验证。利用单细胞（GSE140228）和空间转录组（HRA000437）数据集研究NEDD1及其预测伴侣MZT2B的共表达和空间分布。NEDD1在HCC组织中显著高表达，并与不良预后相关。其过表达可能与启动子低甲基化和异常磷酸化有关。NEDD1敲低可抑制HCC细胞增殖、迁移及体内肿瘤生长。值得注意的是，NEDD1表达与免疫检查点分子（PD-1、CTLA-4）呈正相关，低NEDD1表达与更好的免疫治疗预测应答相关。单细胞和空间转录组学揭示，NEDD1与MZT2B的共表达在特定巨噬细胞亚群（如APOE+）中高度富集，并表现出细胞背景依赖性异质性，提示它们可能在HCC微环境中构成一个动态功能模块。这项多组学研究提示NEDD1可作为HCC潜在的预后生物标志物和治疗靶点。我们提出一种新模型，即NEDD1-MZT2B模块可能在肿瘤细胞和免疫抑制性巨噬细胞中发挥作用，可能影响疾病进展和免疫治疗应答。
Abstract
The neural precursor cell expressed developmentally down-regulated protein 1 (NEDD1) is implicated in tumorigenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to explore the oncogenic role, regulatory mechanisms, and tumor microenvironment interactions of NEDD1 in HCC. Multi-omics analyses were performed using public datasets (TCGA, GEO) and in-house clinical samples. These included expression and survival analysis, epigenetic (DNA methylation) and post-translational (phosphorylation) profiling, functional pathway enrichment, and drug sensitivity prediction. Functional validation was conducted via NEDD1 knockdown in HCC cells and a subcutaneous xenograft model. The co-expression and spatial distribution of NEDD1 and its predicted partner MZT2B were investigated using single-cell (GSE140228) and spatial transcriptomic (HRA000437) datasets. NEDD1 was significantly overexpressed in HCC tissues and correlated with poor prognosis. Its overexpression was potentially linked to promoter hypomethylation and aberrant phosphorylation. NEDD1 knockdown suppressed HCC cell proliferation, migration, and tumor growth in vivo. Notably, NEDD1 expression positively correlated with immune checkpoint molecules (PD-1, CTLA-4), and low NEDD1 expression was associated with better predicted response to immunotherapy. Single-cell and spatial transcriptomics revealed that NEDD1 and MZT2B co-expression was highly enriched in specific macrophage subsets (e.g., APOE+) and exhibited cell context-dependent heterogeneity, suggesting they may constitute a dynamic functional module within the HCC microenvironment. This multi-omics study suggests NEDD1 as a potential prognostic biomarker and therapeutic target in HCC. We propose a novel model wherein the NEDD1-MZT2B module may operate in both tumor cells and immunosuppressive macrophages, potentially influencing disease progression and immunotherapy response.
如何引用
AMA
Yu Chen, Zuyin Wan, Haixiang Xie, Xin Zhou, Tao Peng. Multi-omics analysis of NEDD1 in hepatocellular carcinoma: biological function, prognostic value, and clinical significance.. Scientific reports. 2026; doi:10.1038/s41598-026-42505-z.
APA
Yu Chen, Zuyin Wan, Haixiang Xie, Xin Zhou, Tao Peng (2026). Multi-omics analysis of NEDD1 in hepatocellular carcinoma: biological function, prognostic value, and clinical significance.. Scientific reports. https://doi.org/10.1038/s41598-026-42505-z
GB/T 7714
Yu Chen, Zuyin Wan, Haixiang Xie, Xin Zhou, Tao Peng. Multi-omics analysis of NEDD1 in hepatocellular carcinoma: biological function, prognostic value, and clinical significance.[J]. Scientific reports, 2026 doi:10.1038/s41598-026-42505-z.
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