Zhu Haifeng, Wang Yun, Chen Zunyu, Guo Ruonan, Wu Xiaobai, Jiang Yifan, Shu Yang, Huang Hanpeng
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Transl Cancer Res. 2025 May 30;14(5):3113-3132. doi: 10.21037/tcr-2024-2265. Epub 2025 May 27.
Hypoxia contributes to the proliferation, migration, and chemotherapy resistance of lung adenocarcinoma (LUAD). This study aimed to identify hypoxia-related genes (HRGs) in LUAD that were positively correlated with hypoxia-inducible factor 1 alpha (), to advance the diagnosis and treatment of this specific type of cancer.
The transcriptome data were retrieved from the Gene Expression Omnibus (GEO). Multiple bioinformatics analysis methods were employed to identify HRGs that were upregulated in LUAD samples and positively correlated with the expression of . Machine Learning algorithms were utilized for optimized selection, filtering out core HRGs highly associated with the disease. Finally, experiments confirmed the expression of these core HRGs in LUAD cells under hypoxic conditions.
The study revealed five core HRGs that exhibit a positive correlation with [collagen type I alpha 1 chain (), interleukin 11 (), matrix metallopeptidase 14 (), notch receptor 3 (), and thymocyte differentiation antigen 1 ()]. experiments conducted on A549 cells demonstrated a marked increase in mRNA expression for both the identified core HRGs and following chronic intermittent hypoxia (CIH) treatment. The developed model exhibits substantial predictive efficacy for assessing the prognosis of LUAD patients experiencing concurrent hypoxia.
The five HRGs that we have identified as positively associated with may serve as crucial targets for promoting the progression of LUAD under hypoxic conditions. This discovery offers valuable insights into the diagnosis and treatment of clinical hypoxic disease in patients with LUAD.
缺氧促进肺腺癌(LUAD)的增殖、迁移和化疗耐药性。本研究旨在鉴定LUAD中与缺氧诱导因子1α(HIF-1α)呈正相关的缺氧相关基因(HRGs),以推进这种特定类型癌症的诊断和治疗。
从基因表达综合数据库(GEO)检索转录组数据。采用多种生物信息学分析方法来鉴定在LUAD样本中上调且与HIF-1α表达呈正相关的HRGs。利用机器学习算法进行优化选择,筛选出与疾病高度相关的核心HRGs。最后,实验证实了这些核心HRGs在缺氧条件下LUAD细胞中的表达。
该研究揭示了五个与HIF-1α呈正相关的核心HRGs[I型胶原α1链(COL1A1)、白细胞介素11(IL11)、基质金属蛋白酶14(MMP14)、Notch受体3(NOTCH3)和胸腺细胞分化抗原1(THY1)]。对A549细胞进行的实验表明,在慢性间歇性缺氧(CIH)处理后,所鉴定的核心HRGs和HIF-1α的mRNA表达均显著增加。所建立的模型在评估同时存在缺氧的LUAD患者预后方面具有显著的预测效能。
我们鉴定出的与HIF-1α呈正相关的五个HRGs可能是促进缺氧条件下LUAD进展的关键靶点。这一发现为LUAD患者临床缺氧疾病的诊断和治疗提供了有价值的见解。