Li Ruixi, Zhang Guangquan, Tao Qiang, Wu Ziyun, Liu Xiaoping, Wang Rongrong, Liu Lei, Niu Yiran, Du Kaile, Wu Runpeng, Du Fei, Zheng Xiyan, Li Yingliang, Shi Xianjie
Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
The First Clinical Medical College of Nanchang University, Nanchang, 330031, China.
Discov Oncol. 2025 May 18;16(1):807. doi: 10.1007/s12672-025-02200-3.
Hepatocellular carcinoma (HCC) is a common malignancy associated with high morbidity and mortality rates worldwide. To improve the prognosis of HCC, early diagnosis is crucial. However, to date, little is known about the role of natural killer cell-related genes (NKCRGs) in predicting the prognosis of hepatocellular carcinoma patients. In this study, we identified 24 differentially expressed NKCRGs in HCC specimens from the TCGA dataset, including 22 upregulated genes and 2 downregulated genes. Functional enrichment analysis revealed that these genes were mainly involved in immune response pathways and various cancer-related pathways. Univariate analysis identified 21 prognostic NKCRGs, with eight genes (PAK1, MAP2K2, MAPK3, PLCG1, SHC1, HRAS, NRAS, and MICB) confirmed to be involved in HCC prognosis through Venn diagram analysis. A prognostic model was developed using LASSO-Cox regression, incorporating four genes (MAP2K2, SHC1, HRAS, and NRAS). The model's risk score was significantly associated with overall survival (OS) in both the TCGA and ICGC cohorts. Patients with high-risk scores had poorer OS, as demonstrated by Kaplan-Meier curves and ROC analyses. The risk score was not significantly correlated with gender or age but was higher in patients with advanced tumor grades and stages. Immune status analysis using ssGSEA showed higher enrichment scores for various immune cells and pathways in the high-risk group. Additionally, the risk score was positively correlated with the immune score, indicating its potential role in tumor microenvironment modulation. Expression analysis revealed that HRAS, SHC1, MAP2K2, and NRAS were upregulated in HCC tissues, with higher expressions of HRAS, MAP2K2, and NRAS associated with shorter OS. Knockdown experiments confirmed that silencing NRAS suppressed the proliferation of HCC cells, highlighting its potential as a therapeutic target. Overall, our findings suggest that the identified NKCRGs, particularly NRAS, play crucial roles in HCC progression and could serve as valuable prognostic markers and therapeutic targets.
肝细胞癌（HCC）是一种常见的恶性肿瘤，在全球范围内发病率和死亡率都很高。为了改善HCC的预后，早期诊断至关重要。然而，迄今为止，关于自然杀伤细胞相关基因（NKCRGs）在预测肝细胞癌患者预后中的作用知之甚少。在本研究中，我们从TCGA数据集中鉴定出24个在HCC标本中差异表达的NKCRGs，其中包括22个上调基因和2个下调基因。功能富集分析表明，这些基因主要参与免疫反应途径和各种癌症相关途径。单变量分析确定了21个预后NKCRGs，通过维恩图分析证实有8个基因（PAK1、MAP2K2、MAPK3、PLCG1、SHC1、HRAS、NRAS和MICB）与HCC预后相关。使用LASSO-Cox回归建立了一个预后模型，纳入了4个基因（MAP2K2、SHC1、HRAS和NRAS）。该模型的风险评分在TCGA和ICGC队列中均与总生存期（OS）显著相关。Kaplan-Meier曲线和ROC分析表明，高风险评分的患者OS较差。风险评分与性别或年龄无显著相关性，但在肿瘤分级和分期较高的患者中更高。使用单样本基因集富集分析（ssGSEA）进行的免疫状态分析显示，高风险组中各种免疫细胞和途径的富集分数更高。此外，风险评分与免疫评分呈正相关，表明其在肿瘤微环境调节中的潜在作用。表达分析显示，HRAS、SHC1、MAP2K2和NRAS在HCC组织中上调，HRAS、MAP2K2和NRAS的高表达与较短的OS相关。敲低实验证实，沉默NRAS可抑制HCC细胞的增殖，突出了其作为治疗靶点的潜力。总体而言，我们的研究结果表明，所鉴定的NKCRGs，特别是NRAS，在HCC进展中起关键作用，可作为有价值的预后标志物和治疗靶点。
Comb Chem High Throughput Screen. 2025
Comb Chem High Throughput Screen. 2022
BMC Bioinformatics. 2023-3-9
Nature. 2024-2
Genes (Basel). 2023-8-23
Trends Cancer. 2023-12
Cancer Lett. 2023-8-28
Int J Mol Sci. 2023-5-30
Zotero 插件
