Yan Yongfeng, Chen Kai, Sun Qian
Department of Laboratory, Tianjin Beichen Hospital, Tianjin, China.
Transl Cancer Res. 2025 Mar 30;14(3):2054-2065. doi: 10.21037/tcr-2025-335. Epub 2025 Mar 27.
Hepatocellular carcinoma (HCC) is a lethal tumor. Predicting the prognosis of HCC remains challenging. Cellular senescence, which is one of the hallmarks of cancer, and its related prognostic-gene signature can provide critical information for clinical decision making. Our objective was to investigate the role of cellular senescence in HCC.
The RNA sequencing data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database were obtained. The HCC subtypes and a senescence score model were established to predict the prognosis of HCC.
In this study, patients from TCGA-HCC dataset were stratified into low- and high-risk groups based on cellular senescence-related genes. The analysis of the various subtypes revealed that the distribution of Cluster 1 (C1) was significantly correlated with numerous factors, including age, sex, pathological T stage, tumor node metastasis (TNM) classification, and grade staging. Further, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the upregulated genes in the high-risk C1 group were primarily engaged in pathways related to the cell cycle, DNA replication, cellular senescence, extracellular matrix (ECM)-receptor interactions, and the mechanisms of mismatch repair. Conversely, the 90 downregulated genes were mainly associated with metabolic pathways, chemical carcinogenesis involving DNA adducts, complement and coagulation cascades, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The resultant boxplots revealed significant differences in the populations of immune cells, such as B cells, endothelial cells, natural killer (NK) cells, macrophages, cluster of differentiation (CD)4+ T cells, and CD8+ T cells, in the C1 HCC samples compared to the C2 HCC samples. Additionally, the prognostic outcomes of the HCC patients were predicted using a cellular senescence-related gene model that included , , , , , , , , , , , and .
This study established a prognostic model of HCC based on cellular senescence-related gene expression. Our findings may provide insights that can be used to develop novel potential targeted therapies.
肝细胞癌（HCC）是一种致命性肿瘤。预测HCC的预后仍然具有挑战性。细胞衰老作为癌症的标志之一，及其相关的预后基因特征可为临床决策提供关键信息。我们的目的是研究细胞衰老在HCC中的作用。
获取来自癌症基因组图谱（TCGA）数据库的HCC患者的RNA测序数据和临床信息。建立HCC亚型和衰老评分模型以预测HCC的预后。
在本研究中，基于细胞衰老相关基因，将来自TCGA-HCC数据集的患者分为低风险组和高风险组。对各种亚型的分析表明，簇1（C1）的分布与许多因素显著相关，包括年龄、性别、病理T分期、肿瘤淋巴结转移（TNM）分类和分级分期。此外，京都基因与基因组百科全书（KEGG）分析表明，高风险C1组中上调的基因主要参与与细胞周期、DNA复制、细胞衰老、细胞外基质（ECM）-受体相互作用以及错配修复机制相关的途径。相反，90个下调的基因主要与代谢途径、涉及DNA加合物的化学致癌作用、补体和凝血级联反应以及过氧化物酶体增殖物激活受体（PPAR）信号通路相关。所得箱线图显示，与C2 HCC样本相比，C1 HCC样本中免疫细胞群体，如B细胞、内皮细胞、自然杀伤（NK）细胞、巨噬细胞、分化簇（CD）4 + T细胞和CD8 + T细胞，存在显著差异。此外，使用包含 、 、 、 、 、 、 、 、 、 、 和 的细胞衰老相关基因模型预测了HCC患者的预后结果。
本研究基于细胞衰老相关基因表达建立了HCC的预后模型。我们的研究结果可能为开发新型潜在靶向治疗提供见解。
