Zhang Shixuan, Hu Xiaoxi, Sun Mengzhen, Chen Xinrui, Le Shiguan, Wang Xilu, Wang Jiucun, Hu Zixin
State Key Laboratory of Genetic Engineering, School of Life Sciences & Human Phenome Institute, Fudan University, Shanghai, 200438, China.
Zhangjiang Fudan International Innovation Centre, Human Phenome Institute, Fudan University, Shanghai, China.
Sci Rep. 2025 Apr 15;15(1):12942. doi: 10.1038/s41598-024-84561-3.
Cancer incidence and mortality are lower among high-altitude residents, suggesting that hypobaric hypoxia (HH) might protect against cancer. Our study aimed to develop a pan-cancer prognosis risk model using ADME genes, which are influenced by low oxygen, to explore HH's impact on overall survival (OS) across various cancers. We constructed and validated the model with gene expression and survival data from 8628 samples, using three gene expression databases. AltitudeOmics confirmed HH's significant effects. We employed single-gene prognostic analysis, weighted gene co-expression network analysis, and stepwise Cox regression to identify biomarkers and refine the model. Drugs interacting with the model were explored using LINCS L1000, AutoDockTools, and STITCH. Eight ADME genes significantly altered by HH were identified, revealing their prognostic value across cancers. The model showed lower risk scores linked to better prognosis in 25 cancers, with reduced overall gene expression and decreased tumor mortality risk. Higher T cell infiltration was observed in the low-risk group. Additionally, three potential drugs to modulate our model were identified. This study presents a novel pan-cancer survival prognosis model based on ADME genes influenced by HH, offering new insights into cancer prevention and treatment.
高原居民的癌症发病率和死亡率较低，这表明低压缺氧（HH）可能对癌症具有保护作用。我们的研究旨在利用受低氧影响的药物代谢动力学（ADME）基因开发一种泛癌预后风险模型，以探讨HH对各种癌症总生存期（OS）的影响。我们使用三个基因表达数据库，通过来自8628个样本的基因表达和生存数据构建并验证了该模型。AltitudeOmics证实了HH的显著影响。我们采用单基因预后分析、加权基因共表达网络分析和逐步Cox回归来识别生物标志物并完善模型。使用LINCS L1000、AutoDockTools和STITCH探索与该模型相互作用的药物。确定了8个受HH显著改变的ADME基因，揭示了它们在各种癌症中的预后价值。该模型显示，在25种癌症中，较低的风险评分与较好的预后相关，总体基因表达降低，肿瘤死亡风险降低。在低风险组中观察到较高的T细胞浸润。此外，还确定了三种调节我们模型的潜在药物。本研究提出了一种基于受HH影响的ADME基因的新型泛癌生存预后模型，为癌症预防和治疗提供了新的见解。
