Chen Yan, Chang Li, Hu Ling, Yan Cuiping, Dai Liu, Shelat Vishal G, Yarmohammadi Hooman, Sun Jun
Department of Laboratory, Yangzhou Hongquan Hospital, Yangzhou, China.
Department of Laboratory, Yangzhou Second People's Hospital, Yangzhou, China.
J Gastrointest Oncol. 2024 Aug 31;15(4):1636-1646. doi: 10.21037/jgo-24-405. Epub 2024 Aug 14.
Prior studies indicate that lactylation regulates various biological mechanisms within cancer. However, lactylation-related genes (LRGs) have been found to have limited value in predicting the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to review HCC LRGs using data from The Cancer Genome Atlas (TCGA).
The RNA sequencing data and related clinical information of patients with HCC patients were collected from the TCGA database. A total of 20 LRGs were selected and bioinformatics analysis was performed. A consistency cluster analysis was conducted to classify the HCC tumors. Using a lactylation-related model of HCC, prognosis, immune cell infiltration, and immunotherapy was evaluated.
A total of 4,378 genes were associated with prognosis. Twenty LRGs (i.e., , and ) were identified. The 20 LRGs were used to divide TCGA-HCC patients into low-risk (G1) and high-risk (G2) categories. The upregulated genes in the G1 group primarily participate in the p53 signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cell cycle, while the downregulated genes primarily participate in the glycolysis/gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. The box plots showed a significant difference in the immune cell populations, with a higher abundance of B cells, CD4 T cells, CD8 T cells, neutrophils, macrophages, and myeloid dendritic cells in the G1 than the G2 HCC samples. Further, the box plots showed higher expression levels of seven of the eight immune checkpoint inhibitor (ICI)-related genes in the G1 HCC samples than the G2 samples. There was a significant disparity in the cancer stem cell (CSC) scores between the G1 and G2 TCGA-HCC patients. Additionally, the G1 TCGA-HCC patients had higher tumor immune dysfunction and exclusion (TIDE) scores than the G2 TCGA-HCC patients. The prognosis of the HCC patients was also predicted using a six-LRG model, comprising , and .
Strong correlation between LRGs and tumor classification as well as immunity in patients with HCC was identified. LRG signatures serve as reliable prognostic markers for HCC.
先前的研究表明，乳酰化作用调节癌症中的各种生物学机制。然而，已发现乳酰化相关基因（LRGs）在预测肝细胞癌（HCC）预后方面价值有限。本研究的目的是利用来自癌症基因组图谱（TCGA）的数据对HCC的LRGs进行综述。
从TCGA数据库收集HCC患者的RNA测序数据和相关临床信息。共选择20个LRGs并进行生物信息学分析。进行一致性聚类分析以对HCC肿瘤进行分类。使用HCC的乳酰化相关模型评估预后、免疫细胞浸润和免疫治疗。
共有4378个基因与预后相关。鉴定出20个LRGs（即 、 和 ）。这20个LRGs用于将TCGA-HCC患者分为低风险（G1）和高风险（G2）类别。G1组中上调的基因主要参与p53信号通路、粘着斑、细胞外基质（ECM）-受体相互作用和细胞周期，而下调的基因主要参与糖酵解/糖异生、碳代谢和氨基酸生物合成。箱线图显示免疫细胞群体存在显著差异，G1组中的B细胞、CD4 T细胞、CD8 T细胞、中性粒细胞、巨噬细胞和髓样树突状细胞的丰度高于G2组HCC样本。此外，箱线图显示G1组HCC样本中八个免疫检查点抑制剂（ICI）相关基因中的七个表达水平高于G2组样本。G1和G2 TCGA-HCC患者之间的癌症干细胞（CSC）评分存在显著差异。此外，G1组TCGA-HCC患者的肿瘤免疫功能障碍和排除（TIDE）评分高于G2组TCGA-HCC患者。还使用由 、 和 组成的六LRG模型预测了HCC患者的预后。
确定了LRGs与HCC患者肿瘤分类及免疫之间的强相关性。LRG特征可作为HCC可靠的预后标志物。
