Liang Tu-Liang, Chen Ying, Zhou Nan-Jie, Shu Xiao, Mi Jia-Ning, Ma Gang-Yuan, Xiao Yao, Yang Xi, Huang Chen, Li Jia-Xin, Xie Ying, Yan Pei-Yu, Yao Xiao-Jun, Liu Liang, Pan Hu-Dan, Leung Elaine Lai-Han, Li Run-Ze
State Key Laboratory of Traditional Chinese Medicine Syndrome/Chinese Medicine, Guangdong Laboratory, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, PR China.
Guangzhou Medical University, Guangzhou, 510182, PR China.
NPJ Precis Oncol. 2025 Mar 28;9(1):90. doi: 10.1038/s41698-025-00872-2.
Accurate metabolic biomarkers for lung cancer prognosis remain scarce but crucial. Taurine and proline, two metabolites, are consistently elevated across various cancer stages in previous studies, hinting at their potential role in disease progression. This study is the first to reveal how these metabolites contribute to poor prognosis. Transcriptomic analysis uncovered that taurine and proline downregulated Zinc-α2-glycoprotein (Azgp1), a gene linked to key metabolic pathways. Additionally, Azgp1 could also significantly affect downstream lipid metabolic pathways in lung cancer. Both taurine and proline influenced lipid metabolism via mammalian target of rapamycin (mTOR). When Azgp1 was overexpressed, lung cancer progression slowed significantly, alongside reduced mTOR activity. These findings underscore the pro-cancer role of taurine and proline, highlighting the Azgp1/mTOR axis as a vital, yet overlooked, pathway in lung cancer. This study not only advances our understanding but also identifies new therapeutic avenues.
用于肺癌预后的准确代谢生物标志物仍然稀缺但至关重要。牛磺酸和脯氨酸这两种代谢物在先前的研究中,在各个癌症阶段均持续升高,这暗示了它们在疾病进展中的潜在作用。本研究首次揭示了这些代谢物如何导致不良预后。转录组分析发现,牛磺酸和脯氨酸下调了锌-α2-糖蛋白(Azgp1),这是一种与关键代谢途径相关的基因。此外,Azgp1还可显著影响肺癌的下游脂质代谢途径。牛磺酸和脯氨酸均通过雷帕霉素靶蛋白(mTOR)影响脂质代谢。当Azgp1过表达时,肺癌进展显著减缓,同时mTOR活性降低。这些发现强调了牛磺酸和脯氨酸的促癌作用,突出了Azgp1/mTOR轴作为肺癌中一个重要但被忽视的途径。这项研究不仅增进了我们的理解,还确定了新的治疗途径。