Shaheed Sadr Ul, Al-Eidan Ahood A, Pors Klaus, Patterson Laurence, Sutton Chris W
Nuffield Department of Surgical Sciences and Biomedical Research Centre, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Clin Proteomics. 2025 Oct 31;22(1):41. doi: 10.1186/s12014-025-09565-1.
Cytochrome P450 (CYP450) enzymes are essential for drug metabolism, xenobiotic detoxification, and procarcinogen activation, playing a pivotal role in both normal physiology and cancer biology. Their expression varies significantly across tissues and tumour types, reflecting the metabolic heterogeneity of cancers. Understanding these variations is critical for developing targeted therapies, optimizing drug efficacy, and minimizing toxicity. This study aimed to comprehensively profile CYP450 expression across colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), breast cancer, and hepatic cancer models using proteomic techniques.
We analysed various cancer models (cell lines, xenografts, and patient tissue biopsies) using gel electrophoresis coupled with liquid chromatography-mass spectrometry (GEL-LC-MS). Equal amounts of protein were separated by gel electrophoresis, and the 45-65 kDa molecular weight range was analysed on the Orbitrap Fusion Mass Spectrometer.
Distinct CYP450 expression profiles were observed across cancer types. In CRC, CYP2W1 and CYP2S1 were highly expressed, while CYP1B1 and CYP2W1 were prominent in HNSCC, highlighting their potential as biomarkers and therapeutic targets. Breast cancer models predominantly expressed CYP2J2 and CYP2S1, whereas CYP3A and CYP2C subfamily members were enriched in hepatic cancer, underscoring their roles in xenobiotic metabolism and drug clearance.
This study provides the first comprehensive semi-quantitative proteomic map of CYP450 isoforms across multiple cancer models. The findings reveal metabolic heterogeneity and identify clinically relevant targets, offering a foundation for future functional studies and personalized therapeutic strategies.
细胞色素P450（CYP450）酶对于药物代谢、外源性物质解毒和前致癌物激活至关重要，在正常生理学和癌症生物学中均发挥着关键作用。它们的表达在不同组织和肿瘤类型中差异显著，反映了癌症的代谢异质性。了解这些差异对于开发靶向治疗、优化药物疗效和最小化毒性至关重要。本研究旨在使用蛋白质组学技术全面分析结直肠癌（CRC）、头颈部鳞状细胞癌（HNSCC）、乳腺癌和肝癌模型中CYP450的表达情况。
我们使用凝胶电泳结合液相色谱 - 质谱联用（GEL-LC-MS）分析了各种癌症模型（细胞系、异种移植瘤和患者组织活检样本）。等量蛋白质通过凝胶电泳分离，然后在Orbitrap Fusion质谱仪上分析45 - 65 kDa分子量范围的蛋白质。
在不同癌症类型中观察到了不同的CYP450表达谱。在CRC中，CYP2W1和CYP2S1高表达，而在HNSCC中CYP1B1和CYP2W1显著，突出了它们作为生物标志物和治疗靶点的潜力。乳腺癌模型主要表达CYP2J2和CYP2S1，而CYP3A和CYP2C亚家族成员在肝癌中富集，强调了它们在外源性物质代谢和药物清除中的作用。
本研究提供了首个跨多种癌症模型的CYP450同工型的全面半定量蛋白质组图谱。研究结果揭示了代谢异质性并确定了临床相关靶点，为未来的功能研究和个性化治疗策略奠定了基础。
