Identification Of ANGPT2, FLT3, IGF1, and SPP1 associated with glycolysis and PI3K/Akt signaling pathway in hepatocellular carcinoma.

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-09-20 Epub Date: 2025-07-15 DOI:10.1016/j.gene.2025.149644

Yan Wang, Shiying Feng, Zifan Feng, Jie Yin, Yuzhi Zhang, Hezhao Zhang, Manyu Li, Jia Wu, Rui Zhang

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引用次数: 0

Abstract

Background: Hepatocellular carcinoma (HCC) is a malignant hepatic neoplasm characterized by rapid cellular proliferation facilitated by aerobic glycolysis. Additionally, the PI3K/Akt pathway enhances angiogenesis, thereby promoting the growth of HCC cells. This study aimed to identify biomarkers associated with glycolysis and the PI3K/Akt signaling pathway in HCC.

Method: Differential analysis was conducted on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset to identify differentially expressed genes (DEGs) between tumor and normal tissues. Overlapping DEGs, glycolysis-related genes (GMRGs), and PI3K/Akt pathway-related genes were analyzed to select candidate genes. Biomarkers were determined using ten algorithms within the protein-protein interaction (PPI) network, and their correlation with angiogenesis, autophagy, apoptosis, and Epithelial-Mesenchymal Transition(EMT) was examined. Biomarker expression levels were validated using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR) and compared between HCC and normal tissues in the TCGA-LIHC and GSE14520 datasets.

Results: A total of 7,476 DEGs were identified between tumor and normal tissues, from which 20 candidate genes were selected, leading to the identification of four biomarkers (ANGPT2, FLT3, IGF1, and SPP1) via PPI analysis. These biomarkers were positively correlated with angiogenesis, autophagy, apoptosis, and EMT. In both TCGA-LIHC and GSE14520 datasets, ANGPT2 and SPP1 exhibited higher expression levels in HCC tissues compared to normal tissues. The expression of these biomarkers was further validated through RT-qPCR.

Conclusion: This study identified four biomarkers linked to glycolysis and the PI3K/Akt signaling pathway in HCC, providing a theoretical foundation for HCC treatment.

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肝细胞癌中与糖酵解和PI3K/Akt信号通路相关的ANGPT2、FLT3、IGF1和SPP1的鉴定

背景：肝细胞癌（HCC）是一种以有氧糖酵解促进细胞快速增殖为特征的恶性肝脏肿瘤。此外，PI3K/Akt通路增强血管生成，从而促进HCC细胞的生长。本研究旨在确定HCC中与糖酵解和PI3K/Akt信号通路相关的生物标志物。方法：对肝癌基因组图谱（Cancer Genome Atlas Liver hepatellular Carcinoma, TCGA-LIHC）数据集进行差异分析，鉴定肿瘤与正常组织之间的差异表达基因（Differential expression genes, DEGs）。分析重叠的DEGs、糖酵解相关基因（GMRGs）和PI3K/Akt通路相关基因以选择候选基因。在蛋白质-蛋白质相互作用（PPI）网络中使用十种算法确定生物标志物，并检查它们与血管生成、自噬、细胞凋亡和上皮-间质转化（EMT）的相关性。使用实时定量反转录PCR （RT-qPCR）验证生物标志物的表达水平，并在TCGA-LIHC和GSE14520数据集中比较HCC和正常组织之间的生物标志物表达水平。结果：共鉴定出肿瘤与正常组织之间的7476个deg，从中筛选出20个候选基因，通过PPI分析鉴定出4个生物标志物（ANGPT2、FLT3、IGF1和SPP1）。这些生物标志物与血管生成、自噬、细胞凋亡和EMT呈正相关。在TCGA-LIHC和GSE14520数据集中，ANGPT2和SPP1在HCC组织中的表达水平高于正常组织。通过RT-qPCR进一步验证这些生物标志物的表达。结论：本研究确定了HCC中与糖酵解和PI3K/Akt信号通路相关的4个生物标志物，为HCC的治疗提供了理论基础。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.